La vida media de los nuevos anticoagulantes orales es de · • Historia de dispepsia o riesgo de...

La vida media de los nuevos anticoagulantes orales es de

1 23-26 horas2 15 a 6 horas3 12 horas 4 48 horas

1 2 3 4

42

1717

25

El NOACS que tiene menor eliminacioacuten por viacutea renal

1 Dabigatraacuten2 Apixaban3 Rivaroxaban4 Edoxaban

1 2 3 4

31

7

21

40

Todos los NOACS se caracteriza por lo siguiente excepto

1 No requieren monitoreo de laboratorio

2 Menor o miacutenima interaccioacuten con dieta y medicamentos

3 Disminuyen el riesgo de hemorragia intracraneal

4 El INR refleja fielmente el estado de la anticoagulacioacuten

51 2 3 4 5

02 0

94

4

Los factores de riesgo para el incremento de complicaciones tromboemboacutelicas

1 DM2 Edad mayor de 75

antildeos3 Sexo masculino4 ICC

1 2 3 4

6 13

75

6

INDICACIONES TERAPEacuteUTICAS DE LOS ANTICOAGULANTES ORALES DIRECTOS

(Nuevos anticoagulantes orales)

Panamaacute 28 de agosto de 2015

Rauacutel Izaguirre AacutevilaDepartamento de Hematologiacutea Cliacutenica de Anticoagulantes Orales

Instituto Nacional de Cardiologiacutea Ignacio Chaacutevez

1000 ndash 1400 horasAuditorio Ignacio Chaacutevez Rivera

FARMACODINAacuteMICA Y FARMACOCINEacuteTICA DE LOS ACODImplicaciones terapeacuteuticas

ANTICOAGULANTES ORALES DIRECTOS (De blanco uacutenico)

Una nueva familia de anticoagulantes orales

Anti-IIa( -gatranes)

bull Ximelagatraacutenbull Melagatraacutenbull Dabigatraacutenbull Efegatraacuten

Anti-Xa( -xabanes)

bull Rivaroxabaacutenbull Apixabaacutenbull Edoxabaacutenbull Betrixabaacutenbull Eribaxabaacutenbull Darexabaacutenbull Letaxabaacutenbull Otamixabaacuten

PROPIEDADES DE LOS ANTICOAGULANTES ORALES DIRECTOSNuevos Anticoagulantes Orales Anticoagulantes de blanco uacutenico

DABIGATRAacuteN APIXABAacuteN RIVAROXABAacuteN EDOXABAacuteN

Objetivo IIa Xa Xa Xa

Biodisponibilidad()

6-7 66 67-79 50

Tmax (h) 2-3 1-3 2ndash4 1-3

Vida media 14 ndash 17 h 8 ndash 15 h 7 ndash 13 h 5 ndash 11 h

Efecto de la dieta Retrasa absorcioacuten

No Retrasa absorcioacuten

No

Vigilancia No No No No

Administr 2d 2d 1d 1d

Metabol 80 renal20 hiacutegado

25 renal75 hiacutegado

33-66 renal 35 renal65 hiacutegado

Panorama de estudios cliacutenicos recientes y en desarrollo en fase 3 acerca de ACO

Dabigatraacuten Rivaroxabaacuten Apixabaacuten

Prevencioacuten EVT RE-MODELRE-NOVATERE-MOBILIZERE-SOLVE

RECORD 1RECORD 2RECORD 3RECORD 4MAGELLAN

ADVANCE1ADVANCE 2ADVANCE 3ADOPT

Tratamiento EVT RE-COVER I y IIRE-MEDYRE-SONATE

EINSTEIN-DVTEINSTEIN-PEEINSTEIN-EXT

AMPLIFYAMPLIFY-EXT

Prevencioacuten de EVC en FA RE-LY ROCKET-AF ARISTOTLEAVERROES

Prevencioacuten de eventos secundarios en SICA

RE-DEEM ATLAS 2 APPRAISE-2

National Institutes of Health ClinicalTrialsgovct2resultsterm=apixaban Accessed July 16 2008National Institutes of Health ClinicalTrialsgovct2resultsterm=rivaroxaban Accessed July 16 2008National Institutes of Health ClinicalTrialsgovct2resultsterm=dabigatran Accessed July 16 2008

28 ESTUDIOS FASE 3

NUEVOS ANTICOAGULANTES ORALESIndicaciones aprobadas en Meacutexico y FDA

APIXABAacuteN DABIGATRAacuteN RIVAROXABAacuteNPrevencioacuten ETEV en artroplastiacutea electiva de cadera

radic radic radic

Prevencioacuten ETEV en artroplastiacutea electiva de rodilla

radic radic radic

Prevencioacuten de EVCESen FA

radic radic radic

Tratamiento de la TVP radic radic radicTratamiento de la TEP radic radic radicPrevencioacuten secundaria TVPTEP

radic radic radic

SICA radic en Meacutexico3 rechazos por la FDA

INICIO DEL TRATAMIENTO CON ACOConsideraciones iniciales

bull Es criacutetico explicar al enfermo la importancia del apego con los NAO (vida media maacutes corta)

bull Convencerlo de que no debe descontinuarlos por la raacutepida desaparicioacuten del efecto protector

bull Mantener el apego auacuten durante los viajesbull El enfermo y sus familiares deben recibir informacioacuten

detallada sobre los signos de alerta

bull Se producen defectos en la adherencia en el 25-35 de los pacientes recibiendo tratamientos croacutenicos

bull El incumplimiento puede alcanzar el 50bull La ausencia de monitorizacioacuten incrementa el riesgo de

una mala adherenciabull Debido a su vida media corta los incumplimientos en

la toma de los nuevos anticoagulantes pueden traducirse en una complicacioacuten tromboemboacutelica

bull En pacientes con mala adherencia es preferible utilizar AVK


PACIENTES CON FA NO VALVULAR QUE DEBERIacuteAN PERMANECER CON AVK

bull FA con afectacioacuten valvular estenosis mitral u otra valvulopatiacutea significativa

bull Proacutetesis valvulares o valvuloplastiacuteasbull Buen control del tratamiento anticoagulantebull Historia de dispepsia o riesgo de HGIbull Insuficiencia renal gravebull Pacientes que no desean pasar a los nuevos

anticoagulantes oralesSETH 2013

bull Pacientes con AVK sin control del INR (2-3) a pesar de buen cumplimiento terapeacuteutico

bull TRT lt 60 en los uacuteltimos 6 meses de tratamiento (se excluyen inicios y suspensiones por cirugiacuteas o procedimientos invasivos)

bull Dificultad para acceder al control bioloacutegicobull Hipersensibilidad conocida o contraindicacioacuten a AVKbull Alto riesgo tromboacutetico especialmente si han sufrido un episodio

tromboemboacutelico arterial grave durante el tratamiento con dicumariacutenicos

bull Antecedentes de hemorragia intracranealbull EVC isqueacutemico con alto riesgo de hemorragia intracranealbull Hemorragia grave a pesar de un buen control del INR

CAMBIO DE AVK A NUEVOS ANTICOAGULANTES ORALES

SETH 2013

GRUPOS ESPECIALESIncremento del riesgo de hemorragia

bull Peso lt 60 kgbull Edad gt 75 antildeos gt 80 antildeosbull Creatinina lt 15 mgdLbull Depuracioacuten de Cr lt 50 mLminbull No se recomienda con DepCr lt30 mLminbull Insuficiencia renal incrementa el riesgo de EVC

hemorragia mayor y cualquier causa de mortalidadbull Pacienes con FA + falla renal riesgo altobull Empleo juicioso de NAC Vigilancia maacutes estrecha

ANTICOAGULANTES ORALES DIRECTOS EN FIBRILACIOacuteN AURICULAR

LAS LIMITANTES DE LA WARFARINA CONDUCEN A SUBTRATAMIENTO DE PACIENTES CON FA ELEGIBLES PARA ANTICOAGULACIOacuteN

18

0

20

40

60

80

100

lt 55 55ndash64 65ndash74 75ndash84 ge 85

44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total

1 Go A et al Ann Intern Med 1999131927

FA = fibrilacioacuten auricular

Efecto promedio ponderado en la tasa de riesgo (HR)de los NAO vs warfarina

Puntos de desenlace

Cualquier NAO (dabigatraacuten 110 mg apixabaacuten rivaroxabaacuten) vs warfarina


Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000

EVC isqueacutemico o de tipo incierto 0983 0866 1116 0788 0878 0771 1000 0051

EVC hemorraacutegico 0485 0373 0632 0000 0474 0363 0619 0000

Mortalidad por todas las causas 0890 0825 0961 0003 0880 0815 0950 0001

IM 0953 0810 1120 0557 0949 0807 1116 0525

Hemorragia mayor ISTH 0831 0765 0902 0000 0875 0806 0950 0001

HIC 0465 0378 0572 0000 0490 04000 0601 0000

1 Lip GYH et al J Am Coll Cardiol 201260738-746

Soacutelo los puntos de desenlace disponibles en todos los estudios se reportanES = embolia sisteacutemica EVC = evento vascular cerebral HIC = hemorragia intracraneal HR = razoacuten de riesgo IC = intervalo de confianza IM = infarto de miocardio ISTH = International Society on Thrombosis and Haemostasis (Sociedad Internacional de Trombosis y Hemostasia NAO = nuevo anticoagulante oral

19

Apixabaacuten Warfarina HR (IC del 95 ) Valor de P

Ndeg de pacientes antildeo (Ndeg de eventos)

CHADS2 Interaccioacuten 04457

1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)

CHA2DS2VASc Interaccioacuten 01210

1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)

HAS-BLED Interaccioacuten 09422

0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114

ARISTOTLE EVC o embolia sisteacutemica seguacuten los puntajes de riesgo iniciales

025 05 100 20

Mejor apixabaacuten Mejor warfarina

40EVC = evento vascular cerebral HR = razoacuten de riesgo IC = intervalo de confianza

Adaptado de Lopes RD et al Lancet 20123801749-1758

Eficacia y seguridad consistente de apixabaacuten en adultos mayores

1 Halvorsen S et al Eur Heart J 2014 35(28)1864-1872

Hemorragia intracraneal

Favorece a la warfarina

Favorece al apixaban

Reduccioacuten del riesgo relativo con Apixabaacuten en adultos mayores

RR

R v

s W

arfa

rina

Antildeos antildeos

EVCES Hemorragia mayor Hemorragia IC

Consistencia de la eficacia y seguridad incluso en pacientes con alto riesgo de eventos vasculares cerebrales o hemorragias




RR

R v

s W

arfa

rina

Poblacioacuten generalCHA2DS2VAScge3

CHADS2ge3HAS-BLEDge3

Reduccioacuten del riesgo relativo con Apixabaacuten de acuerdo con CHADS2 CHA2DS2VASc y HAS-BLED en la

evaluacioacuten de baseEVCES Hemorragia mayor

La superioridad del Apixabaacuten vs warfarina es consistente independientemente del grado de insuficiencia renal

1 Hohnloser SH et al Eur Heart J 201233(22)2821-2830 Tasa estimada de filtracioacuten glomerular (Cockroft-Gault mlmin)



Reduccioacuten del riesgo relativo con apixabaacuten de acuerdo con TFG

RR

R v

s W

arfa

rina

EVCES Hemorragia mayor

Eficacia y seguridad consistente de apixabaacuten en adultos mayores (gt75 antildeos) de acuerdo con TFG


tasa estimada de filtracioacuten glomerular(Cockroft-Gault mlmin)



Reduccioacuten del riesgo relativo con apixabaacuten de acuerdo con TFG en pacientes de edad avanzada (gt75 antildeos)

RR

R v

s W

arfa

rina


Nuevos anticoagulantes orales en pacientes ge 75 antildeos

25

Evento vascular cerebral

Hemorragia mayor

Ensayo RR [IC de 95]

ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]

Modelo de efectos fijos 077 [067-089]

Modelo de efectos aleatorios 077 [067-089]

05 075 1251

1 Lega JC et al PLoS One 2014 9(3)e91398


ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871

NOAC en pacientes con DCr lt50 mlmin

26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808

NOAC en pacientes con insuficiencia cardiaca

27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0

CARACTERIacuteSTICAS DE LOS PACIENTES Y PRINCIPALES RESULTADOS DE LOS ESTUDIOS CLIacuteNICOS EN FA

CRITERIO RE-LY ROCKET-AF ARISTOTLE

NAO investigado Dabigatraacuten Rivaroxabaacuten Apixabaacuten

Pacientes (N) 18113 14264 18201

EVC previo () 20 55 19

TRT con warfarina () 64 55 62

Mortalidad (antildeo) 3736 45 35

Hemorragia mayor (antildeo)

2833 56 21

Cualquier hemorragia(antildeo)

147166 207 181

Hemorragia IC (antildeo) 023032 05 033

CRITERIOS DE EXCLUSIOacuteN EN LOS ESTUDIOS CLIacuteNICOS CON LOS NUEVOS ANTICOAGULANTES ORALES (1)



Proacutetesis valvular Siacute Siacute SiacuteEnf Valvular relevante Siacute Siacute SiacuteEVC dentro de 14 d 14 d 7 dEVC grave dentro de 6 m 3 m NIDep Cr lt30 mLmin lt30 mLmin lt25 mLminPFHs incremento doble 3 veces Doble

Embarazo Siacute Siacute SiacuteCirugiacutea uacuteltimo mes Siacute Siacute NICirugiacutea planeada 3 m Siacute Siacute SiacuteH IC espinal ocular retroperitoneal hemartrosis Siacute Siacute Siacute



CA reciente (3 antildeos) Siacute NI NI

Esperanza de vida NI lt 2 antildeos lt 1 antildeo

Contrandicacioacuten W Siacute Siacute Siacute

Endocarditis infec Siacute Siacute Siacute

Nivel Hb lt 10 gdL lt 10 gdL lt 9 gdL

Plaquetas lt 100000uL lt 90000uL lt 100000uL

Aspirina gt 100 mgd gt 100 mgd gt 165 mgd


Ensayos cliacutenicos con los NAOresumen de los resultados de la fase III

1 Connolly SJ et al N Engl J Med 20093611139-1151 2 Patel MR et al N Engl J Med 2011365883-891 3 Granger CB et al N Engl J Med 2011365981-992

Resultados frente a warfarina Dabigatraacuten1

110 mgDabigatraacuten1

150 mg Rivaroxabaacuten2 Apixabaacuten3

en EVCembolia sisteacutemica No inferior Superior No inferior Superior

en EVC No Siacute No Siacute

en EVC isqueacutemicono especificado No Siacute No No

en EVC hemorraacutegico Siacute Siacute Siacute Siacute

en EVC incapacitantemortal No Siacute No Siacute

en mortalidad vascular No Siacute No No

en mortalidad por todas las causas No No No Siacute

en hemorraggia importante Siacute No No Siacute

en HIC Siacute Siacute Siacute Siacute

en hemorragia GI No Siacute Siacute No

en suspensioacuten del tratamiento No No No Siacute

EVC = evento vascular cerebral GI = gastrointestinal HIC = hemorragia intracraneal NAO = nuevo anticoagulante oral

Sin comparaciones directas ndash Soacutelo con fines ilustrativos ndash adaptado de referencias 1-3

31

1 De Caterina R et al J Am Coll Cardiol 2012591413-1425

NAO vs warfarina en FANV puntos de desenlace

Eficacia(EVC o embolia sisteacutemica)

Seguridad(hemorragia mayor)

14

0

121

08060402

14

0

121

08060402

Dabigatraacuten 150 mg BID


Rivaroxabaacuten 20 mg QD

Apixabaacuten 5 mg BID





HR

(IC

95

)

HR

(IC

95

)

BID = dos veces al diacutea EVC = evento vascular cerebral FANV = fibrilacioacuten auricular no valvular HR = razoacuten de riesgo IC = intervalo de confianza QD = una vez al diacutea

32

ANTICOAGULANTES ORALES DIRECTOSTRATAMIENTO DE LA ENFERMEDAD TROMBOEMBOacuteLICA

VENOSA

RECOVER 2009Dabigatraacuten

RECOVER II 2013Dabigatraacuten

EINSTEIN 2010Rivaroxabaacuten

EINSTEIN EXT 2011Rivaroxabaacuten

EINSTEIN DVT-EP 2013Rivaroxabaacuten

EINSTEIN EP 2012Rivaroxabaacuten

AMPLIFY 2013Apixabaacuten

AMPLIFY EXY 2013Apixabaacuten

ANTICOAGULANTES ORALES DE BLANCO UacuteNICOESTUDIOS EN ENFERMEDAD TROMBOEMBOacuteLICA VENOSA

RE-SONATE RE-MEDY 2013Dabigatraacuten

HNF HBPM AVK 3 6 12 mesesETAPA AGUDA PREVENCIOacuteN SECUNDARIA

ACO DE BLANCO UacuteNICOHNF HBPM

ACO-BUETAPA AGUDA

PREVENCIOacuteN SECUNDARIA

TRATAMIENTO TRADICIONAL NUEVA ERA DE LA ANTICOAGULACIOacuteN

Estudios Fase III de los NOACs para el tratamiento del TEV

1 Agnelli et al N Engl J Med 2013369799-808 2 Agnelli et al N Engl J Med 2013368699-708 3 Schulman et al N Engl J Med 20093612342-522 4 Schulman et al Circulation 2014129764-72 5 Schulman et al N Engl J Med 2013368709-18 6 The HOKUSAI-VTE Investigators N Engl J Med 20133691406-15 7 Bauersachs et al N Engl J Med 20103632499-510 8 Buumlller et al N Engl J Med 20123661287-97

Dabigatraacuten y edoxaban no

evaluados en el tratamiento

inicial

Dabigatraacuten (RE-COVER)3

Dabigatraacuten (RE-COVER II)4

Dabigatran (RE-SONATE)5

Dabigatran (RE-MEDY)5

Edoxaban (HOKUSAI-VTE)6

Rivaroxaban (EINSTEIN-DVT)7

Rivaroxaban (EINSTEIN-PE)8Rivaroxaban (EINSTEIN-Extensioacuten)7

No hay datos con Edoxaban

Apixaban en TVP amp EP (AMPLIFY)1 Apixaban en TVP amp EP (AMPLIFY-EXT)2

Antagonista de la Vitamin KParenteral

TVP trombosis de vena profunda EP embolismo pulmonar

Tratamiento indefinido se refiere a anticoagulacioacuten que se continuacutea sin una fecha de finalizacioacuten programada pero que se puede terminar debido a un aumento en el riesgo de sangrado o a un cambio en la preferencia del paciente hospitalizado

LWMH fondaparinux Donde esteacute aprobado se puede hacer la terapia inicial rivaroxaban oral Los sujetos inscritos en el estudio han cumplido 6 ndash 12 meses de terapia con anticoagulacioacuten

Inicial(0 a 7 diacuteas)

Largo plazo(7 diacuteas to 3ndash6 meses)

Prolongado(3ndash6 meses a indefinido)

Estudios de NOACs para el tratamiento del TEV agudo Resumende resultados

1 Agnelli et al N Engl J Med 2013369799-808 2 Schulman et al N Engl J Med 20093612342-52 3 Schulman et al Circulation 2014129764-72 4 Buumlller et al N Engl J Med 20133691406-15 5 Bauersachs et al N Engl J Med20103632499-2510 6 Buumlller et al N Engl J Med 20123661287-97

TEV Recurrente o muerte relacionada con TEV Hemorragia Mayor Hemorragia Mayor o NMCR

ApixabanAMPLIFY1

DabigatranRE-COVER2

DabigatranRE-COVER II3

EdoxabanHOKUSAI-VTE4

Rivaroxaban EINSTEIN-DVT5

RivaroxabanEINSTEIN-PE6

RR riesgo relativo HR iacutendice de riesgo NMCR no mayor cliacutenicamente relevante comp comparador

No existen estudios uno a uno por lo tanto no se pueden hacer comparaciones entre los agentes

01 1 10NAO mejor Comp mejor

RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003

P value for non-inferiority

01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)

lt0001for superiority

035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value

HR 062(045ndash084) Not reported

NAO mejor Comp mejor NAO mejor Comp mejor

Chart1

Data
8
65
5
35
2
05

Calculations

Remember the first cells of columns A through E must be filled according to the type of outcome The current formating is for rates
Dark grey columns and cells do not require any formatting
Fill this cell with the number of studies you are including
Start here fill the studies names then fill the rest of the information Light gray columns need adjustment according to study size

Forest Plot

The X axis can be formated to logartimic scale if needed just right click on it and click on Format Axis You can also chose the intervals and starting and ending points
Dark grey columns do not require formatting
Either if you have analyzed data using spreadsheet 1 or other software just enter the outcome and SE in columns D and ERemember to adjust the X axis for better visualization (see comment on cell E14)
This set of cells will provide the central tendency line on the graph

Forest Plot

Data
Central Tendency

Plan1

MB Stroke amp SE_dabi150



Central Tendency

Sheet1

Queacute sabemos acerca de las tasas de hemorragia en los estudios de tratamiento del TEV agudo Datos de dabigatraacuten (RE-COVER)

Schulman et al N Engl J Med 20093612342-52

Hemorragia Mayor

Hemorragia Mayor o NMCR

P=038

P=0002

201273

241266

711273

1111266

HR = 082 (95 CI 045ndash148) HR = 063 (95 CI 047ndash084)

WarfarinaDabigatran WarfarinaDabigatran

(Resultado primario de seguridad)

Graacutefico1

AC Parenteral Dabigatran (N=1273)
AC Parenteral Warfarin (N=1266)
Pacientes con evento
16
56
19
88
16
19
56
88

Sheet1

Queacute sabemos acerca de las tasas de hemorragia en los estudios de tratamiento del TEV agudo Datos de dabigatraacuten (RE-COVERII)

Schulman et al Circulation 2014129764-72

Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

Parenteral AC Dabigatran (N=1280)
Parenteral AC Warfarin (N=1288)
12
50
17
79
12
17
5
79

Sheet1

Queacute sabemos acerca de las tasas de hemorragia en los estudios de tratamiento del TEV agudo Datos de rivaroxabaacuten (EINSTEIN-DVT)

Bauersachs et al N Engl J Med 20103632499-510

P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban

Warfarina o acenocumarol

VKARivaroxaban

HemorragiaMayor

Hemorragia Mayor o NMCR(Resultado primario de seguridad)

Graacutefico1

Rivaroxaban (N=1718)
EnoxaparinVKA (N=1711)
08
81
12
81
08
12
81
81

Sheet1

Queacute sabemos acerca de las tasas de hemorragia en los estudios de tratamiento del TEV agudo Datos de rivaroxabaacuten (EINSTEIN-EP)

Buumlller et al N Engl J Med 20123661287-97

P=023

P=0003

2492412

2742405

262412522405



VKARivaroxaban VKARivaroxaban

Hemorragia Mayor


Graacutefico1

Enoxaparin VKA (N=2405)
11
103
22
114
11
22
103
114

Sheet1

Queacute sabemos acerca de las tasas de hemorragia en los estudios de tratamiento del TEV agudo Datos de apixaban (AMPLIFY)

Agnelli et al N Engl J Med 2013369799-808

Plt0001 (para superioridad)

Plt0001

152676492689

1152676

2612689

Apixaban ApixabanWarfarin Warfarin

RR = 031 (95 CI 017ndash055) RR = 044 (95 CI 036ndash055)

HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
Enoxaparin Warfarin (N=2689)
06
43
18
97
06
18
43
97

Sheet1

Hemorragia Mayor o NMCR (HR [IC 95])No hay comparaciones uno a uno estas comparaciones no se han hecho en un estudio uno a uno

Eficacia y seguridad de los NOACs vs comparador en TEV aguda

Cohen et al Adv Ther 201431473-93

00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE

RivaroxabanEINSTEIN-PE

RivaroxabanEINSTEIN-DVT

ApixabanAMPLIFY

DabigatranRE-COVER 1


2

Menos hemorragia

Maacutes recurrencias Maacutes recurrencias

Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

TRATAMIENTO DE LA ETEV CON NAOSEstudios fase III

Resultados de eficacia y seguridad

ESTUDIO RE-COVER I Y II EINSTEIN DVT Y PE AMPLIFY HOKUSAI VTE

ACO Dabigatraacuten Rivaroxabaacuten Apixabaacuten Edoxabaacuten

Duracioacuten 6 m 3 6 oacute 12 m 6 m 12 m

Pacientes 5153 8282 5395 8292

DAB W RIVA W APIXA W EDOXA W

TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)

Eficacia y seguridad de NOACs vs placebo en TEV


0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])

Hemorragia Mayor o NMCR (HR [IC 95])

Apixaban 5 mgAMPLIFY-Ext

Apixaban 25 mgAMPLIFY-EXT

DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02

No hay comparaciones uno a uno estas comparaciones no son hechas en estudio uno a uno

2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento

SecundarioIdiopaacutetico

Factores de riesgo

Fase aguda

Evitar la extensioacutenEvitar la embolia

Prevencioacuten secundaria3 ndash 6 meses

Evitar el 2do evento

TRATAMIENTO ANTICOAGULANTE

iquestSuspenderRiesgo de trombosis 15 a 3 antildeos

iquestContinuarRiesgo de hemorragia 3 anual 13 fatal

2do evento

iquestCoacutemo los identifico

Factores de riesgo

TRATAMIENTO DE LA ENFERMEDAD TROMBOEMBOacuteLICA VENOSARetos a los que nos enfrentamos

Extensioacuten

TEPTVP

Sin Choque o hipotensioacuten

Con Choque o hipotensioacuten

Servicio de Urgencias

Meacutedico urgencioacutelogoMeacutedico internistaMeacutedico familiar

Meacutedico intensivistaMeacutedico internistaNeumoacutelogoCardioacutelogo

Meacutedico internistaNeumoacutelogoAngioacutelogoMeacutedico urgencioacutelogoMeacutedico familiar

FASE AGUDA PREVENCIOacuteN SECUNDARIA

EXTENSIOacuteN

Meacutedico internistaNeumoacutelogoAngioacutelogoCardioacutelogoMeacutedico familiarHematoacutelogoOncoacutelogoReumatoacutelogo

ESTABLECER LAS CAUSASProvocadaFactor transitorioFactor permanenteNo provocadaTrombofiliaCaacutencer


3 ndash 10 diacuteas3 ndash 6 meses

IndefinidaDe por vida

MEDICOS INVOLUCRADOS EN EL TRATAMIENTO DE LA ETEV

TrombolisisAnticoagulacioacuten

SEGURIDAD DE LOS ACOD EN CIRUGIacuteAORTOPEacuteDICA

DIFERENCIAS EN LA DEFINICIOacuteN DE HEMORRAGIA

bull Los estudios que excluyeron la hemorragia en el sitio quiruacutergico de la definicioacuten mostraron una tasa de hemorragia 10 veces menor que los estudios que la incluyeron

bull En 11 estudios llevados en Europa la enoxaparina se administroacute 40 mgd 12 horas antes o la noche anterior a la cirugiacutea En 3 estudios se diacutea post operatorio

bull En 5 estudios llevados en EUA la enoxaparina se administroacute 30 mg2d iniciando de 12 a 24 horas despueacutes de la cirugiacutea

bull Con excepcioacuten de los estudios de rivaroxabaacuten (RECORD 1 ndash 4) los demaacutes incluyeron la hemorragia en el sitio quiruacutergico en la definicioacuten de hemorrgia mayor asociada con disminucioacuten de la Hb o necesidad de transfusioacuten

bull El estudio ADVANCE-1 incluyoacute la hemorragia sospechada por cliacutenica que se corroboroacute por imagen

48

J Thromb Haemos 819662010

69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4

Rivaroxabaacuten Enoxaparina

REC-4 REC-3 REC-2RTR RTR RTC

Cualquier TEV o muerte de cualquier causa Hemorragia mayor o HNMCR

Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC

RESULTADOS DE LOS ESTUDIOS FASE III CON RIVAROXABAacuteN

311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25

Dabigatraacuten 220 mg Enoxaparina

RE-MOB RE-MOD RE-NOV 2

RTR RTR RTC

Cualquier TEV o muerte de cualquier causa Hemorragia mayor

Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC

RESULTADOS DE LOS ESTUDIOS FASE III CON DABIGATRAacuteN

9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5

6Apixabaacuten Enoxaparina

ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)

RESULTADOS DE LOS ESTUDIOS FASE III CON APIXABAacuteN

Resultados de NAC vs Enoxaparina en prevencioacuten de ETV posterior a cirugiacutea ortopeacutedica

Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten

Menor eficaciaMayor hemorragia

Menor eficaciaMenor hemorragia

Mayor eficaciaMenor hemorragia

Mayor eficaciaMayor hemorragia

11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE

Riesgo relativo de todas ETV

Riesgo relativo de Hemorragia mayor + CRNM

Tendencia para mejoriacutea de eficacia vs Enoxaparina

Tendencia para reduccioacuten hemorragia vs Enoxaparina

9ena Conferencia de Consenso ACCP Recomendaciones (2012)

9vna CONFERENCIA CONSENSO ACCP 2012Cirugiacutea ortopeacutedica

APIXABAacuteN EN CIRUGIacuteA ORTOPEacuteDICA Ventajas de la ventana de inicio (12 ndash 24 horas)

CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN

Estabilizacioacuten post-anesteacutesicaDetectar hemorragia quiruacutergicaObservar flujo de la heridaCorregir teacutecnica operatoriaManejo de nausea y voacutemitoMovilizacioacuten de cateacuteteres

VENTANA DE INICIO

El inicio entre 12 y 24 horas despueacutes mantiene la misma eficacia que enoxaparina

-24 -12 6 12 24

Horas

iquestLA DOSIFICACIOacuteN 1 O 2 VECES AL DIacuteA AFECTA LOS RESULTADOS Y EL APEGO AL TRATAMIENTO

CYP = citocromo P450 Dep Cr = depuracioacuten de creatinina FA = fibrilacioacuten auricular gp-P = glucoproteina P PNS = polimorfismo de nucleoacutetido simple

1 Gong IY et al Can J Cardiol 201329S24-S33

Tiempo desde uacuteltima dosis (h)Tiempo desde uacuteltima dosis (h)

Tiempo desde uacuteltima dosis (h)

Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)

Paciente tiacutepico con FAInsuficiencia hepaacutetica moderadaDep Cr 30 mlminDep Cr 50 mlminInhibicioacuten de gp-PCYP3A4 Etnia japonesaInduccioacuten de gp-PCYP3A1

Plas

ma

[Api

xabaacute

n] (n

gm

l)

Edad (93 vs 68)CES1 SNP (rs2244613)Induccioacuten de gp-P

Dep Cr 30 mlminDep Cr 50 mlminInhibicioacuten de gp-P

Paciente tiacutepico con FA

Peso (lt50 kg)Induccioacuten de gp-PCYP3A1

Inhibicioacuten de gp-PCYP3A4Dep Cr lt30 mlmin


Perfiles de concentracioacuten plasmaacutetica de dabigatraacuten rivaroxabaacuten y apixabaacuten en pacientes con FA

Inhibicioacuten de la generacioacuten de trombina mediante inhibidores del factor Xa

La inhibicioacuten de la generacioacuten de trombina variacutea a traveacutes del tiempo con diferentes inhibidores del factor Xa

Aumento de riesgo de hemorragiacutea

BetrixabaacutenApixabaacutenRivaroxabaacutendagger

d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c

cAumento de riesgo de

trombosis

Betrixabaacuten 80 mg QD con dosis de carga Apixabaacuten 25 mg BID daggerRivaroxabaacuten 10 mg QD1 US Securities and Exchange Commission Submission Filed April 12 2013 Disponible en httpwwwsecgovArchivesedgardata1269021000119312513153305d436765ds1htm Consultado el 18 de agosto de 2014

ACODAnaacutelisis de 1 o 2 dosis al diacutea

bull A mayor diferencia entre pico y valle mayor fluctuacioacuten de los niveles plasmaacuteticos

bull Las fluctuaciones mayores podriacutean tener consecuencias cliacutenicas hemorragia y tromboembolia

bull Parece razonable reducir la variacioacuten pico-valle para balancear el riesgo-beneficio

ANTICOAGULANTES ORALES DIRECTOS

Anaacutelisis de 1 o 2 dosis al diacutea

bull Una o maacutes dosis de ACOD omitidas pueden incrementar el riesgo de EVC

bull Esto es vaacutelido cuando un faacutermaco con una vida media corta (12 horas o menos) se administra 1 vezd

bull De acuerdo a la evaluacioacuten farmacocineacutetica la omisioacuten de 1 dosis se traduce enndash 2 horas en riesgo si es 2 vecesdndash 10 horas en riesgo si es 1 vez d

bull Al olvidar una dosis el esquema de 2d es maacutes favorable que 1d



bull La dosificacioacuten 2d muestra una tendencia a mayor eficacia (prevencioacuten de EVC ES) y mejor perfil de seguridad (HIC) en comparacioacuten con la dosificacioacuten de 1dbull Los NOA muestran una reduccioacuten en la mortalidad por cualquier causa de 10 en comparacioacuten con warfarinabull Los esquemas de 2d tienen menor HRscomparados con rivaroxabaacuten 2015 mgd pero no con edoxabaacuten 6030 mgd

PLOS|ONE



DOSIFICACIOacuteN DE LOS ACOD UNA Vs DOS VECES DIacuteA

iquestHay diferencia

Apego constanteOlvido de una dosis en el esquema

de 2 vecesdiacutea



El olvido de una dosis en el esquema de 1diacutea equivale a 3 dosis omitidas

en el esquema de 2d

Efecto de una dosis extra en las dos dosificaciones

dagger No hay diferencia significativa entre 1 o dos dosis al diacutea

El apego al tratamiento no es diferente entre 1 o 2 dosis al diacutea

Apixabaacuten vs warfarina

Dabigatraacuten 110 mg vs warfarina


Rivaroxabaacuten vs warfarina

Abandono del tratamiento

A favor de warfarinaA favor de NAO

INTERRUPCIOacuteN DEL TRATAMIENTO CON NAOsAnaacutelisis de 101801 pacientes (18 estudios)

Interrupcioacuten del tratamiento con NAO por efectos adversos en FA


Interrupcioacuten del tratamiento con NAO por efectos adversos en TVPTEP


Interrupcioacuten del tratamiento con NAO por cualquier causa en SICA

ConclusionesAproximadamente la mitad de los enfermos con FA no estaacuten

protegidos contra el EVC Los inconvenientes de los AVK y el temor a la hemorragia contribuyen

Los NAO causan menor hemorragia intracraneana que la warfarina

La dosificacioacuten 2d muestra una tendencia a mayor eficacia (prevencioacuten de EVC ES) y mejor perfil de seguridad (HIC) en comparacioacuten con la dosificacioacuten de 1d

La omisioacuten de una dosis de un faacutermaco con vida media de 12 horas cuando se administra cada 24 horas equivale a 3 dosis omitidas si se administrara cada 12 horas

70

Conclusiones (continuacioacuten) Las recomendaciones (ACCP 2012) dan maacutes importancia a evitar las

complicaciones hemorraacutegicas Aparte de la warfarina las guiacuteas de AHAASA 2012 recomiendan los

siguientes NAO en FA apixabaacuten (I B) dabigatraacuten (I B) rivaroxabaacuten (IIa evidencia B)

La importancia relativa de la hemorragia puede variar de acuerdo con las condiciones cliacutenicas subyacentes

Considerar siempre la eficacia en forma paralela a la hemorragia En caso de agentes con eficacia similar LA HEMORRAGIA VIENE A SER LO MAacuteS IMPORTANTE

Los ACOD han mostrado utilidad en FA y tratamiento y prevencioacuten de ETEV Se deben considerar grupos especiales de riesgo falla renal edad avanzada

bajo peso Los puntos maacutes importantes para el mejor aprovechamiento de los NAO

son asegurar el apego y conocer la funcioacuten renal y hepaacutetica

71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora





INDICACIONES TERAPEacuteUTICAS DE LOS ANTICOAGULANTES ORALES DIRECTOS(Nuevos anticoagulantes orales)

Nuacutemero de diapositiva 6


ANTICOAGULANTES ORALES DIRECTOS (De blanco uacutenico)Una nueva familia de anticoagulantes orales




























Estudios de NOACs para el tratamiento del TEV agudo Resumen de resultados







TRATAMIENTO DE LA ETEV CON NAOSEstudios fase IIIResultados de eficacia y seguridad



























Conclusiones

Conclusiones (continuacioacuten)






Apixaban (N=2676) Enoxaparin Warfarin (N=2689)

Major 06 18

Major or CRNM 43 97

CRNM 38 8

To resize chart data range drag lower right corner of range

Major Major

Major or CRNM Major or CRNM

Rivaroxaban (N=2412) Enoxaparin VKA (N=2405)

Major 11 22

Major or CRNM 103 114

CRNM 95 98


Major Major


Rivaroxaban (N=1718) EnoxaparinVKA (N=1711)

Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major


Parenteral AC Dabigatran (N=1280) Parenteral AC Warfarin (N=1288)

Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major


AC Parenteral Dabigatran (N=1273) AC Parenteral Warfarin (N=1266)

Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN

Study Events Sample Size Outcome SE CI lower CI upper Rate CI lower CI upper

Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 Rate- CI lower CI Upper-Rate 95 CI

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 lower upper

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 Apixaban (AMPLIFY) 6 084 06 118

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 Dabigatran (RE-COVER) 5 11 065 184

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 DAbigatran (RE-COVER II) 4 108 064 18

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 Edoxaban (HOKUSAI-VTE) 3 089 07 113

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 Rivaroxaban (DVT) 2 068 044 104

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 Rivaroxaban (PE) 1 112 075 168

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586

Central Tendency Graph 85

0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374

This work is licensed under a Creative Common license Attribution 30 Unported (CC BY 30)

More information at httpcreativecommonsorglicensesby30

In a nutshell you may use this work any way you want as long as you cite the source

19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212

Central Tendency Graph

0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374

Theoretical Study Prevalence of variable A in population B - metanalysis of 10 cross sectional studies

Study Events Sample Size Outcome (es) SE Var w wes w(es2) w2 wv wves wv(es2) wv2

Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879

es (fixed) 01971298014 es (random) 01964276191

SEes (fixed) 00030177085 SEes (random) 00047417407

CI (fixed) 01912150928 02030445101 CI (random) 01871338074 02057214308

084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037



1 2 3 4

31

7

21

40






51 2 3 4 5

02 0

94

4




1 2 3 4

6 13

75

6












Anti-Xa( -xabanes)





Biodisponibilidad()

6-7 66 67-79 50

Tmax (h) 2-3 1-3 2ndash4 1-3




No













AMPLIFYAMPLIFY-EXT





28 ESTUDIOS FASE 3



radic radic radic


radic radic radic


radic radic radic


radic radic radic























SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037






51 2 3 4 5

02 0

94

4




1 2 3 4

6 13

75

6












Anti-Xa( -xabanes)





Biodisponibilidad()

6-7 66 67-79 50

Tmax (h) 2-3 1-3 2ndash4 1-3




No













AMPLIFYAMPLIFY-EXT





28 ESTUDIOS FASE 3



radic radic radic


radic radic radic


radic radic radic


radic radic radic























SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037




1 2 3 4

6 13

75

6












Anti-Xa( -xabanes)





Biodisponibilidad()

6-7 66 67-79 50

Tmax (h) 2-3 1-3 2ndash4 1-3




No













AMPLIFYAMPLIFY-EXT





28 ESTUDIOS FASE 3



radic radic radic


radic radic radic


radic radic radic


radic radic radic























SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037












Anti-Xa( -xabanes)





Biodisponibilidad()

6-7 66 67-79 50

Tmax (h) 2-3 1-3 2ndash4 1-3




No













AMPLIFYAMPLIFY-EXT





28 ESTUDIOS FASE 3



radic radic radic


radic radic radic


radic radic radic


radic radic radic























SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037




Biodisponibilidad()

6-7 66 67-79 50

Tmax (h) 2-3 1-3 2ndash4 1-3




No













AMPLIFYAMPLIFY-EXT





28 ESTUDIOS FASE 3



radic radic radic


radic radic radic


radic radic radic


radic radic radic























SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037








AMPLIFYAMPLIFY-EXT





28 ESTUDIOS FASE 3



radic radic radic


radic radic radic


radic radic radic


radic radic radic























SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037



radic radic radic


radic radic radic


radic radic radic


radic radic radic























SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037






















SETH 2013






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037






18

0

20

40

60

80

100


44

58 61 57

35

Edad (antildeos)

Uso

de

war

farin

a en

pa

cien

tes

eleg

ible

s (

)

55 Uso total




Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037


Puntos de desenlace



Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

Efecto promedio

ponderado HR

IC 95 liacutemite

inferior

IC 95 liacutemite

superiorValor P

EVC o ES 0856 0772 0948 0003 0793 0714 0881 0000

EVC 0847 0756 0949 0004 0769 0684 0864 0000




IM 0953 0810 1120 0557 0949 0807 1116 0525


HIC 0465 0378 0572 0000 0490 04000 0601 0000



19




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037




1 6183 074 (44) 087 (51)

2 6516 124 (74) 137 (82)

ge 3 5502 195 (94) 280 (132)


1 1604 062 (10) 053 (8)

2 3771 085 (30) 067 (24)

ge 3 12826 148 (172) 203 (233)


0ndash1 7461 092 (65) 114 (79)

2 6568 139 (83) 181 (109)

ge 3 4172 173 (64) 214 (77)

General 18201 127 (212) 160 (265) 00114


025 05 100 20










RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037







RR

R v

s W

arfa

rina

Antildeos antildeos






RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037





RR

R v

s W

arfa

rina










RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037






RR

R v

s W

arfa

rina








RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037







RR

R v

s W

arfa

rina



25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037


25


Hemorragia mayor


ARISTOTLE 072 [054-096]

RELY 110 mg 088 [066-117]

RELY 150 mg 067 [049-091]

ROCKET 081 [064-102]



05 075 1251



ARISTOTLE 067 [055-082]

RELY 110 mg 102 [085-123]

RELY 150 mg 117 [098-140]

ROCKET 066 [050-087]



05 075 1251

P Het = 057 I2 = 0

P Het = lt0001 I2 =871


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037


26


Hemorragia mayor


ARISTOTLE 079 [056-112]

RELY 110 mg 089 [061-130]

RELY 150 mg 047 [030-074]

ROCKET 088 [065-119]



05 075 1251



ARISTOTLE 052 [039-069]

RELY 110 mg 101 [079-129]

RELY 150 mg 100 [078-128]

ROCKET 082 [057-118]



05 075 1251

P Het = 012 I2 = 494

P Het = 0001 I2 = 808


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037


27


Hemorragia mayor


ARISTOTLE 088 [064-121]

RELY 110 mg 099 [069-142]

RELY 150 mg 075 [051-110]

ROCKET 093 [075-115]



05 075 1251



ARISTOTLE 063 [048-082]

RELY 110 mg 083 [064-108]

RELY 150 mg 079 [060-104]

ROCKET 075 [058-096]



05 075 1251P Het = 051 I2 = 0

P Het = 074 I2 = 0




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037




Pacientes (N) 18113 14264 18201





2833 56 21


147166 207 181



































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037


































31





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037





14

0

121

08060402

14

0

121

08060402









HR

(IC

95

)

HR

(IC

95

)


32


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037


VENOSA













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037













ACO-BUETAPA AGUDA







inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037





inicial




















ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037




ApixabanAMPLIFY1

DabigatranRE-COVER2








RR 084(060ndash118)

HR 110(065ndash184)

HR 108(064ndash180)

HR 089(070ndash113)

HR 068(044ndash104)

HR 112(075ndash168)

lt0001

lt0001

lt0001

lt0001

lt0001

0003


01 1 10

RR 031(017ndash055)

HR 082(045ndash148)

HR 069(036ndash132)

HR 084(059ndash121)

HR 065(033ndash130)

HR 049(031ndash079)


035

021

0003

P value

not reported

not reported

RR 044(036ndash058)

HR 063(047ndash084)

HR 081(071ndash094)

HR 097(076ndash122)

HR 090(076ndash107)

lt0001

0004for superiority

077

023

lt0002

P value



Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037

Chart1

Data
8
65
5
35
2
05

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




084 034 024

11 074 045

108 072 044

089 024 019

068 036 024

112 056 037

Calculations


Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374



Author 1 year 404 2002 02017982018 00100398358 00001007983 9920801980198 2002 404 98422311930301 50282233527918 10146864308331 2047618971312 252830300855612

Author 2 year 58 353 0164305949 00215744281 00004654559 21484310344828 353 58 461575590992866 17745125290278 2915629651094 47905529678 314889471567659

Author 3 year 187 944 01980932203 00144860109 00002098445 47654331550802 944 187 227093531555378 32475586723521 643319355646 1274372028663 105466373303696

Author 4 year 258 1410 01829787234 00113917577 00001297721 77058139534884 1410 258 593795686857761 43888283486158 8030622084701 1469432977201 192618142736135

Author 5 year 451 2103 02144555397 0010098317 0000101976 98062283813747 2103 451 961621150676791 4998622740714 10719823376424 2298925507735 249862293039828

Author 6 year 430 2420 01776859504 00085687774 00000734239 136195348837209 2420 430 185491730448891 58308002148066 10360512778376 1840917559794 339982311449893

Author 7 yeat 669 3100 02158064516 00083435595 0000069615 143647234678625 3100 669 206345280308159 59632395723616 1286905572229 2777225251036 355602261973787

Author 8 year 52 251 02071713147 00287294922 00008253837 12115576923077 251 52 146787204178994 10828806249199 2243418027722 464771862317 117263044782681

Author 9 year 1535 7790 01970474968 00050294064 00000252949 395336156351791 7790 1535 156290676519008 81054336018348 15971554016452 31471547388 656980538737518

Author 10 year 241 1274 01891679749 00121853805 00001484835 6734755186722 1274 241 453569274250788 4055765201908 7672208898429 1451336220189 164492313730077

k 10 Sums 109810895370416 21647 4285 228285768016322 444758648593323 87362882420279 17250810413828 236104978746158

df 9

v 00000980791

Q 177311882912 Qv 90327421718

I2 492419805587 I2v 03624831879




Forest Plot


Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212


Author 1 year 404 2002 02017982018 00100398358 01821201237 02214762799 11 201798201798 19678078139 19678078139

Author 2 year 58 353 0164305949 00215744281 012202007 0206591828 10 164305949008 42285879001 42285879001

Author 3 year 187 944 01980932203 00144860109 01697006389 02264858018 9 198093220339 2839258145 2839258145

Author 4 year 258 1410 01829787234 00113917577 01606508782 02053065686 8 182978723404 22327845158 22327845158

Author 5 year 451 2103 02144555397 0010098317 01946628384 0234248241 7 214455539705 19792701255 19792701255

Author 6 year 430 2420 01776859504 00085687774 01608911467 01944807542 6 177685950413 16794803741 16794803741

Author 7 yeat 669 3100 02158064516 00083435595 01994530751 02321598281 5 215806451613 16353376533 16353376533

Author 8 year 52 251 02071713147 00287294922 015086151 02634811195 4 207171314741 5630980478 5630980478

Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334 3 197047496791 09857636592 09857636592

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206 2 189167974882 23883345687 23883345687

Summary 0196374 00047 0187162 0205586 1 196374 09212 09212


0 196374

1 196374

2 196374

3 196374

4 196374

5 196374

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374

Forest Plot

Data
Central Tendency

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374




19678078139 19678078139

42285879001 42285879001

2839258145 2839258145

22327845158 22327845158

19792701255 19792701255

16794803741 16794803741

16353376533 16353376533

5630980478 5630980478

09857636592 09857636592

23883345687 23883345687

09212 09212

Plan1




Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374







Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN










Author 9 year 1535 7790 01970474968 00050294064 01871898602 02069051334

Author 10 year 241 1274 01891679749 00121853805 01652846292 02130513206

Summary 0196374 00047 0187162 0205586


0 196374 8 084 06 118 024 034

1 196374 65 11 065 184 045 074

2 196374 5 108 064 18 044 072

3 196374 35 089 07 113 019 024

4 196374 2 068 044 104 024 036

5 196374 05 112 075 168 037 056

6 196374

7 196374

8 196374

9 196374

10 196374

11 196374

12 196374


Central Tendency

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

NaN NaN

118 06

184 065

18 064

113 07

104 044

168 075

NaN NaN

NaN NaN

Sheet1



Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor




Hemorragia Mayor


P=038

P=0002

201273

241266

711273

1111266




Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


Graacutefico1

16
56
19
88
16
19
56
88

Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219


Mayor Mayor


Sheet1



Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major



Mayor 16 19

Major or CRNM 56 88

Todos 161 219




Valor Pno reportado

Valor Pno reportado

151280

221288

641280

1021288



HemorragiaMayor



Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major


Graacutefico1

12
50
17
79
12
17
5
79

Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221


Major Major


Sheet1



P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major



Major 12 17

Major or CRNM 5 79

Any 156 221




P=077

P=021

1391718

1381711141718 201711


VKARivaroxaban


VKARivaroxaban

HemorragiaMayor


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major


Graacutefico1

08
81
12
81
08
12
81
81

Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7


Major Major


Sheet1



P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major



Major 08 12

Major or CRNM 81 81

CRNM 73 7




P=023

P=0003

2492412

2742405

262412522405




Hemorragia Mayor


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major


Graacutefico1

11
103
22
114
11
22
103
114

Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98


Major Major


Sheet1




Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major



Major 11 22


CRNM 95 98





Plt0001

152676492689

1152676

2612689



HemorragiaMayor



Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major


Graacutefico1

Apixaban (N=2676)
06
43
18
97
06
18
43
97

Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8


Major Major


Sheet1




00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Major 06 18

Major or CRNM 43 97

CRNM 38 8





00

1

Recu

rren

cia

de T

EV (H

R [IC

95

])

1 2

EdoxabanHOKUSAI-VTE



ApixabanAMPLIFY



2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia






Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones












Pacientes 5153 8282 5395 8292


TEP recurrente () 24 22 21 23 23 27 16 19

HR (95) IC 109 (076-157) 089 (066-119) 084 (060-118) 082 (060-114)

Hemorragia Mayor ()

14 20 10 17 06 18 14 16

HR (95) IC 073 (048-111) 054 (037-079) 031 (017-055) 084 (059-121)

HM + NMCR () 53 85 94 100 43 97 85 103

HR (95) IC 062 (05-076) 093 (081-106) 044 (036-055) 081 (071-094)



0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones









0 2 654310

1

Recu

rren

cia

TEV

(HR

[IC 9

5 ])




DabigatranRE-SONATE

to 1170Rivaroxaban

EINSTEIN-Ext02


2

Menos hemorragia


Maacutes hemorragia

Menos recurrencias

Maacutes hemorragia

Menos recurrencias

Menos hemorragia

1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones







1er evento


Factores de riesgo

Fase aguda







2do evento


Factores de riesgo


Extensioacuten

TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones







TEPTVP








EXTENSIOacuteN















48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones














48


69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones







69

96

112

101

181

37

93

0

2

4

6

8

10

12

14

16

18

20

333 32

34

23

2725

0

05

1

15

2

25

3

35

4




Even

tos (

)

Even

tos (

)

REC-1RTC


REC-1RTC


311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones







311

364

677

253

377

6788

0

5

10

15

20

25

30

35

40

06

15

2

141413

16

09

0

05

1

15

2

25



RTR RTR RTC


Even

tos (

)

Even

tos (

)

RE-NOV

RTC


REC-1RTC


9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones







9

151

14

88

244

39

0

5

10

15

20

25

30

29

35

4845

485

0

1

2

3

4

5


ADV-1 ADV-2 ADV-3

RTR RTR RTC

ADV-1 ADV-2 ADV-3

RTR RTR RTC


Even

tos (

)

Even

tos (

)



Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones








Rivaroxabaacuten

Dabigatraacuten

Apixabaacuten





11 12 14 16 1802 04 06 08

12

14

16

18

02

04

06

08

ADVANCE-2 ADVANCE-1

Enoxoparina

RE-MOBILIZE








CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones










CIRUGIacuteA

EnoxaPre Op

Dabi6 h

Riva6 h

Apixa19 h

OBSERVACIOacuteN


VENTANA DE INICIO


-24 -12 6 12 24

Horas






Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones












Plas

ma

[Dab

igat

raacuten]

(ng

ml)

Plas

ma

[Riv

arox

abaacuten

] (ng

ml)


Plas

ma

[Api

xabaacute

n] (n

gm

l)












d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones











d

e in

hibi

cioacuten

de

la g

ener

acioacute

n de

trom

bina 100

80

60

40

20

00 20 40 60

Horas

c


trombosis















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones




















PLOS|ONE






de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones










de 2 vecesdiacutea




en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones










en el esquema de 2d





















70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones


























70









71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones















71




1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones










1 2 3 4

0000

15

Conteste ahora



1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones









1 2 3 4

0000

15Conteste ahora






51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones












51 2 3 4 5

00 000

15Conteste ahora




1 2 3 4

0000

15Conteste ahora






































































Conclusiones










1 2 3 4

0000

15Conteste ahora






































































Conclusiones







	Apixaban (N=2676)		Enoxaparin Warfarin (N=2689)

Major		06		18

Major or CRNM		43		97

CRNM		38		8

	To resize chart data range drag lower right corner of range

	Rivaroxaban (N=2412)		Enoxaparin VKA (N=2405)

Major		11		22

Major or CRNM		103		114

CRNM		95		98

	To resize chart data range drag lower right corner of range

	Rivaroxaban (N=1718)		EnoxaparinVKA (N=1711)

Major		08		12

Major or CRNM		81		81

CRNM		73		7

	To resize chart data range drag lower right corner of range

	Parenteral AC Dabigatran (N=1280)		Parenteral AC Warfarin (N=1288)

Major		12		17

Major or CRNM		5		79

Any		156		221

	To resize chart data range drag lower right corner of range

	AC Parenteral Dabigatran (N=1273)		AC Parenteral Warfarin (N=1266)

Mayor		16		19

Major or CRNM		56		88

Todos		161		219

	To resize chart data range drag lower right corner of range

		NaN		NaN

		NaN		NaN

		NaN		NaN

		NaN		NaN

		NaN		NaN

		NaN		NaN

		118		06

		184		065

		18		064

		113		07

		104		044

		168		075

		NaN		NaN

		NaN		NaN

Study		Events		Sample Size		Outcome	SE		CI lower		CI upper		Rate	CI lower		CI upper

Author 1 year		404		2002		02017982018	00100398358		01821201237		02214762799				Rate- CI lower		CI Upper-Rate					95 CI

Author 2 year		58		353		0164305949	00215744281		012202007		0206591828									lower		upper

Author 3 year		187		944		01980932203	00144860109		01697006389		02264858018							Apixaban (AMPLIFY)	6		084		06	118

Author 4 year		258		1410		01829787234	00113917577		01606508782		02053065686							Dabigatran (RE-COVER)	5		11		065	184

Author 5 year		451		2103		02144555397	0010098317		01946628384		0234248241							DAbigatran (RE-COVER II)	4		108		064	18

Author 6 year		430		2420		01776859504	00085687774		01608911467		01944807542							Edoxaban (HOKUSAI-VTE)	3		089		07	113

Author 7 yeat		669		3100		02158064516	00083435595		01994530751		02321598281							Rivaroxaban (DVT)	2		068		044	104

Author 8 year		52		251		02071713147	00287294922		015086151		02634811195							Rivaroxaban (PE)	1		112		075	168

Author 9 year		1535		7790		01970474968	00050294064		01871898602		02069051334

Author 10 year		241		1274		01891679749	00121853805		01652846292		02130513206

Summary				0196374		00047	0187162		0205586

	Central Tendency				Graph			85

	0		196374					8		084		06	118	024		034

	1		196374					65		11		065	184	045		074

	2		196374					5		108		064	18	044		072

	3		196374					35		089		07	113	019		024

	4		196374					2		068		044	104	024		036

	5		196374					05		112		075	168	037		056

	6		196374

	7		196374

	8		196374

	9		196374

	10		196374

	11		196374

	12		196374



This work is licensed under a Creative Common license Attribution 30 Unported (CC BY 30)

More information at httpcreativecommonsorglicensesby30

In a nutshell you may use this work any way you want as long as you cite the source

		19678078139		19678078139

		42285879001		42285879001

		2839258145		2839258145

		22327845158		22327845158

		19792701255		19792701255

		16794803741		16794803741

		16353376533		16353376533

		5630980478		5630980478

		09857636592		09857636592

		23883345687		23883345687

		09212		09212

Theoretical Study Prevalence of variable A in population B - metanalysis of 10 cross sectional studies

Study	Events	Sample Size	Outcome (es)		SE		Var		w		wes		w(es2)	w2		wv		wves		wv(es2)	wv2

Author 1 year	404	2002	02017982018		00100398358		00001007983		9920801980198		2002		404	98422311930301		50282233527918		10146864308331		2047618971312	252830300855612

Author 2 year	58	353	0164305949		00215744281		00004654559		21484310344828		353		58	461575590992866		17745125290278		2915629651094		47905529678	314889471567659

Author 3 year	187	944	01980932203		00144860109		00002098445		47654331550802		944		187	227093531555378		32475586723521		643319355646		1274372028663	105466373303696

Author 4 year	258	1410	01829787234		00113917577		00001297721		77058139534884		1410		258	593795686857761		43888283486158		8030622084701		1469432977201	192618142736135

Author 5 year	451	2103	02144555397		0010098317		0000101976		98062283813747		2103		451	961621150676791		4998622740714		10719823376424		2298925507735	249862293039828

Author 6 year	430	2420	01776859504		00085687774		00000734239		136195348837209		2420		430	185491730448891		58308002148066		10360512778376		1840917559794	339982311449893

Author 7 yeat	669	3100	02158064516		00083435595		0000069615		143647234678625		3100		669	206345280308159		59632395723616		1286905572229		2777225251036	355602261973787

Author 8 year	52	251	02071713147		00287294922		00008253837		12115576923077		251		52	146787204178994		10828806249199		2243418027722		464771862317	117263044782681

Author 9 year	1535	7790	01970474968		00050294064		00000252949		395336156351791		7790		1535	156290676519008		81054336018348		15971554016452		31471547388	656980538737518

Author 10 year	241	1274	01891679749		00121853805		00001484835		6734755186722		1274		241	453569274250788		4055765201908		7672208898429		1451336220189	164492313730077

k	10			Sums		109810895370416		21647		4285		228285768016322		444758648593323	87362882420279		17250810413828		236104978746158

df	9

								v		00000980791

Q	177311882912		Qv		90327421718

I2	492419805587		I2v		03624831879

es (fixed)	01971298014		es (random)		01964276191

SEes (fixed)	00030177085		SEes (random)		00047417407

CI (fixed)	01912150928	02030445101		CI (random)		01871338074		02057214308

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La vida media de los nuevos anticoagulantes orales es de · • Historia de dispepsia o riesgo de...

Documents

Transcript of La vida media de los nuevos anticoagulantes orales es de · • Historia de dispepsia o riesgo de...

Chart1

Calculations

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MB Stroke amp SE_dabi150

MB Stroke amp SE_dabi150

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Forest Plot

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MB Stroke amp SE_dabi150

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Calculations

Forest Plot

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MB Stroke amp SE_dabi150

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MB Stroke amp SE_dabi150

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