Post on 09-Jan-2016
description
DROGAS ANTITROMBÓTICAS
CONGRESO PARAGUAYO DE HEMATOLOGÍA 2011
Dra. Ana María Otero
HEPARINA
1916 HOWEL Y MACFARLAIN 1935 TRATAMIENTO DE LA ETV SALVÓ MUCHAS VIDAS PROVOCÓ MUCHAS MUERTES HASTA HOY SE EMPLEA Y ES ACEPTADA POR
ORGANISMOS INTERNACIONALES
WARFARINA
1945 ANTICOAGULANTE COMPLEJO SALVÓ MUCHAS VIDAS PROVOCÓ MUCHAS MUERTES AÚN HOY SE USA POR ESTUDIOS DE
EVIDENCIA COMO EFECTIVA PREVENCIÓN SECUNDARIA DE LA ETV PREVENCIÓN DE LA EMBOLIA SISTÉMICA
HBPM
1972 ESTUDIO DE KAKKAR SEPARACIÓN ACTIVIDAD ANTI Xa DE LA
ANTI TROMBINA (IIa) 1980 DESARROLLO DE LAS DIFERENTES
HBPM
NUMEROSOS ESTUDIOS DE EVIDENCIA EFECTIVA SEGURA EN LA PREVENCIÓN Y
EL TRATAMIENTO
•Lancet 1972; 2: 101-106.
HBPM
HAN CAMBIADO LOS TRATAMIENTOS ANTITROMBÓTICOS
HAN DESARROLLADO LA PREVENCIÓN PRIMARIA DE LA ETE
SON MUY SEGURAS, SON EFECTIVAS LLEVAN MAS DE 20 AÑOS DE USO MASIVO A
NIVEL MUNDIAL
EPÍDEMIOLOGÍA
TROMBOSIS PRIMERA CAUSA DE MUERTE E INCAPACIDAD
REPERCUSIÓN PERSONALREPERCUSIÓN FAMILARREPERCUSIÓN SOCIAL
PREVENCIÓN DE LA TROMBOSIS
SE PUEDE SE DEBE NO SIEMPRE SE HACE SITUACIONES DE RIESGO MAYOR RIESGO
CIRUGÍA ORTOPÉDICA MAYOR EMBOLIA POR FA ETV EN PACIENTE MEDICOS HOSPITALIZADOS CIRUGÍA MAYOR ASOCIACIÓN DE FACTORES
DROGA ANTITROMBOTICA IDEAL
EFECTIVA SEGURA NO REQUIERA CONTROLES VIA ORAL NO INTERFERENCIAS BAJO COSTO SIN EFECTOS SECUNDARIOS POSEA ANTÍDOTO PARA CASO DE
SANGRADO
DROGA ANTITROMBOTICA IDEAL
NO EXISTE
NUEVAS DROGAS
SINTÉTICASVIA ORALACCIÓN ESPECÍFICA SOBRE UN
FACTOR DE LA COAGULACIÓNRELACIÓN DIRECTA DOSIS EFECTONO NECESIDAD DE CONTROL
BIOLÓGICO ….(?)
NUEVAS DROGAS LAS MAS ESTUDIADADAS (2011)
ETEXILATO DE DABIGATRANRIVAROXABANAPIXABANOTRAS DROGAS VIENEN LLEGANDO
12
WARFARINA ETEXILATO DABIGATRAN RIVAROXABAN
APIXABAN
INHIBEVITAMINA K
E-REDUCTASA TROMBINA FACTOR X FACTOR X
ABSORCIÓN ORAL
99% 67% 60-80% 80%
T (max) 72-96 h 2 h 2.5-4 h 3 h
VIDA MEDIA 40 h 14-17 h5-9 h SANOS, 9-13 h VIEJOS
8-15 h
MONITOREO INR- NO NECESITA? NO NECESITA? NO NECESITA?
ADMINIST. 1/D 1/D o 2 /D 1/D o 2 /D 2/D
MET/ELIMIN.CYTOCHOMO
P45080% RENAL 20% BILIAR
66% RENAL 33% BILIAR
25% RENAL 75% BILIAR
ANTÍDOTO O TRAT.SANGRADO
VIT. K PLASMA
CONSIDERAR PCC O rVIIa
CONSIDERAR PCC O rVIIa
CONSIDERAR PCC O rVIIa
LABORAT. PT/INRECARIN CLOTTING
TIMEANTI FACTOR Xa
ANTI-FACTOR XA
INTERACCIÓN CON DROGAS
CYP 2C9, 1A2, and 3A4
Potent P-gp inhibiDORs/inducers; PPIs decrease
absorción
Potent P-gp inhibitors/inducer
s; CYP3A4 inhibitors
Potent P-gp inhibitors/induc
ers; CYP3A4 inhibitors
COMPARACION DE LA WARFARINA CON LOS NUEVOS ANTICOAGULANTES ORALES
ESTUDIOS CLÍNICOS
DROGA
PREVEN.
STROKE FA
ETV y PREV TRATAMIENTO
PROFILAXIS CIRUGIA ORTOPÉDICA MAYOR
DABIGATRAN
I. DE LA TROMB
RELY RECOVER
REMEDY
RE-MOBILIZE
RE-MODEL
RE-NOVATE
RIVAROXABAN
INHIBIDOR FXa
ROCKET AF EINSTEIN PE
EINSTEIN DVT
EINSTEIN-EXT
MAGELLAN
RECORD 1
RECORD 2
RECORD 3
RECORD 4
APIXABAN
INHIBIDOR FACTOR Xa
AVERROES (ASA)
ARISTOTLE (W)
AMPLIFY
AMPLIFY-EXT
ADVANCE 1
ADVANCE 2
ADVANCE 3
0.1 0.2 0.5 1 2 5 10
Wolowacz et al. Thromb Haemost 2009.
Favours Enoxaparin
Favours Dabigatran
RE-MOBILIZE 188/604 163/643 30mg BIDRE-MODEL 183/503 193/512 40mg QDRE-NOVATE 53/880 60/897 40mg QD
Study or sub-category
Dabigatran etexilate220 mg QD
n/N
Enoxaparin
n/N dose
RR [95% CI]
1.23 [1.03, 1.47]0.97 [0.82, 1.13]0.90 [0.63, 1.29]
Random Effects AnalysisTotal (95% CI) 1987 2052Test for overall effect: Z = 0.47 (P = 0.64)
1.05 [0.87, 1.26]
RR
Analysis is based on the 220 mg QD dose of dabigatran etexilate.
Dabigatran in Orthopedics
Dabigatran approved for VTE prophylaxis post TJR in Canada June 2008y en Europa
EndpointRivaroxaban
(%)
Enoxaparin
(%)HR or RR(95% CI)
Total VTE (DVT, PE, death)
4.26 9.43 RR 0.46
(0.39, 0.54)
Major VTE (proximal DVT, PE, VTE death)
0.68 2.74 RR 0.25
(0.17, 0.37)
Symptomatic VTE or death
0.57 1.32 HR 0.42
(0.29, 0.63)
Major bleeding event 0.39 0.21HR 1.84
(0.94, 3.62)
Major or CRNM bleeding event
3.19 2.55HR 1.25
(1.01, 1.54)
Major bleeding combined with surgical-site bleeding events
1.80 1.37HR 1.31
(0.99, 1.73)
Levitan et al. ASH 2009.
Rivaroxaban in OrthopedicsRECORD 1 - 4
Rivaroxaban approved for VTE prophylaxis post TJR in Canada 2008 y en Europa
KNEE REPLACEMENT1
APIXABAN 2.5 MG PO BID FOR 10 – 14 DAYS
VS ENOXAPARIN 30 MG SC BID STARTING POST-OP
FOR 10 - 14 DAYSFOLLOW-UP: 60 DAYS
N=3195
KNEE REPLACEMENT2
APIXABAN 2.5 MG PO BID FOR 10 – 14 DAYS
VS ENOXAPARIN 40 MG SC QD FOR 10–14 DAYS
FOLLOW-UP: 60 DAYS N=3057
~10,000 patients randomized
1. Lassen, et al. N Engl J Med. 2009.2. Lassen et al. Lancet 2010. 3. Lassen et al. Intl Congress on Thrombosis 2010.
ADVANCE 1 ADVANCE 2HIP REPLACEMENT3
APIXABAN 2.5 MG PO BID FOR 10 – 14 DAYS
VS ENOXAPARIN 40 MG SC
QD FOR 35 DAYS
FOLLOW-UP: 60 DAYS
N=3866
ADVANCE 3
Apixaban in OrthopedicsADVANCE 1 – 3
All VTE/Death
Major VTE Major Bleed
Apix Enox Apix Enox Apix Enox
ADVANCE 1 (TKR)
9.0% 8.9% 2.1% 1.6% 0.7% 1.4%
ADVANCE 2 (TKR)
15.1% 24.4% 1.1% 2.2% 0.6% 0.9%
ADVANCE 3 (THR)
1.4% 3.9% 0. 5% 1.1% 0.8% 0.7%
Apixaban in OrthopedicsADVANCE 1 – 3
• Did not meet prespecified criterion for noninferiority vs enoxaparin 30 mg BID in TKR (ADVANCE 1)
• Superior to enoxaparin 40 mg once daily in THR and TKR (ADVANCE 2 & 3)
1. Lassen, et al. N Engl J Med. 2009. 2. Lassen et al. Lancet 2010. 3. Lassen et al. Intl Congress on Thrombosis 2010.
Enoxaparin Abs. Risk Diff.Outcome- n/N (%) Apixaban 40 mg QD (95% CI)
Major VTE 23/3394 51/3394 -0.76 (0.7) (1.5) (-1.23 to -0.30)
VTE Death 2/4236 0/4228 0.05 (0.05) (0) (-0.02 to 0.11)
Non-Fatal PE 5/4236 5/4228 0.0 (0.12) (0.12) (-0.15 to 0.15)
Sx Proximal DVT 2/4236 5/4228 -0.07 (0.05) (0.12) (-0.19 to 0.05)
Asx Proximal DVT 14/3386 41/3385 -0.62 (0.41) (1.21) (-1.00 to -0.24)
Sx Distal DVT Only 2/4236 7/4228 -0.12 (0.05) (0.17) (-0.26 to 0.02)
Favors Enox
Favors Apixa
-1.5 0 0.5-0.5-1.0
Apixaban in OrthopedicsADVANCE 2 & 3
Raskob et al. ASH 2010 Abstract #192.
Apixaban Enoxaparin AbsoluteOutcome- N (%) (n=4,174) (n=4,167) Diff (95% CI)
MAJOR BLEED 31 (0.74) 32 (0.77) -0.02 (-0.40 to 0.35)
Non-Surgical Site 5 (0.12) 5 (0.12)
Surgical Site 26 (0.62) 27 (0.65) -0.02 (-0.37 to 0.32)
Before 1st Post-Op Dose 17 (0.41) 11 (0.26)
After 1st Post-Op Dose 9 (0.22) 16 (0.38) -0.17 (-0.40 to 0.07)
MAJOR BLEED OR CRNM 182 (4.36) 206 (4.94) -0.58 (-1.49 to 0.32)
Non-Surgical Site 47 (1.13) 51 (1.22)
Surgical Site 135 (3.23) 155 (3.72) -0.49 (-1.27 to 0.30)
Before 1st Post-Op Dose 42 (1.01) 33 (0.79)
After 1st Post-Op Dose 93 (2.23) 122 (2.93) -0.70 (-1.38 to -0.02)
Apixaban in OrthopedicsADVANCE 2 & 3
Raskob et al. ASH 2010 Abstract #192.
PROFILAXIS EN CIRUGÍA ORTOPEDICA MAYOR. CONCLUSI0NES
Los nuevos anticoagulantes orales son similares a la enoxaparina en eficacia y en riesgo de sangrado en prevención de la ETV en cirugía de cadera y rodilla. Dabigatran 220 mg once daily
Rivaroxaban 10 mg once daily
Apixaban 2.5 mg twice daily
Ninguno fue aprobado en EEUU por la FDA pero SI están aprobados por la EMEA y en Canadá.
ESTUDIOS CLÍNICOS
DROGA
PREVEN.
STROKE FA
ETV y PREV TRATAMIENTO
PROFILAXIS CIRUGIA ORTOPÉDICA MAYOR
DABIGATRAN
I. DE LA TROMB
RELY RECOVER
REMEDY
RE-MOBILIZE
RE-MODEL
RE-NOVATE
RIVAROXABAN
INHIBIDOR FXa
ROCKET AF EINSTEIN PE
EINSTEIN DVT
EINSTEIN-EXT
MAGELLAN
RECORD 1
RECORD 2
RECORD 3
RECORD 4
APIXABAN
INHIBIDOR FACTOR Xa
AVERROES (ASA)
ARISTOTLE (W)
AMPLIFY
AMPLIFY-EXT
ADVANCE 1
ADVANCE 2
ADVANCE 3
NUEVOS ANTICOAGULANTES EN LA PREVENCIÓN DEL
STROKE
Fibrilación Auricular NO valvular
ESTUDIOS CLÍNICOS
DROGA
PREVEN.
STROKE FA
ETV y PREV TRATAMIENTO
PROFILAXIS CIRUGIA ORTOPÉDICA MAYOR
DABIGATRAN
I. DE LA TROMB
RELY RECOVER
REMEDY
RE-MOBILIZE
RE-MODEL
RE-NOVATE
RIVAROXABAN
INHIBIDOR FXa
ROCKET AF EINSTEIN PE
EINSTEIN DVT
EINSTEIN-EXT
MAGELLAN
RECORD 1
RECORD 2
RECORD 3
RECORD 4
APIXABAN
INHIBIDOR FACTOR Xa
AVERROES (ASA)
ARISTOTLE (W)
AMPLIFY
AMPLIFY-EXT
ADVANCE 1
ADVANCE 2
ADVANCE 3
DABIGATRAN (RELY) 150 mg dos veces por día es tan eficáz como la warfarina pero,
al precio de un mayor riesgo de sangrado-. 110 mg dos veces al día es comparable la eficacia pero menor
riesgo de sangrado Menos HC que con la warfarina
RIVAROXABAN (ROCKET AF) 20 mg una vez al día, es comparable a la warfarina sin
necesidad de monitoreo. Menos riesgo de HC comparado a la wafarina.
APIXABAN (ABERROES ARISTÓTELES) Aberroes: 5 mg dos veces por dia es más eficáz que la aspirina
en pacientes que no toleran la warfarina. Aristoteles: Comparación con la warfarina está pendiente
stroke
Connolly et al. NEJM 2009. Mahaffey et al AHA 2010. Connolly et al ESC 2010.
DABIGATRAN (APROVADO POR LA FDA) 150 mg dos veces por día es tan eficáz como la
warfarina pero, al precio de un mayor riesgo de sangrado-.
110 mg dos veces al día es comparable pero menor riesgo de sangrado. Menos HC
RIVAROXABAN 20 mg una vez al día es comparable a la warfarina sin
necesidad de monitoreo
Menos riesgo de HC comparado a la wafarina
APIXABAN 5 mg dos veces por dia es más eficáz que la aspirina
en pacientes que no toleran la warfarina. Aristotle: August 28 at the European Society of Cardiology 2011
meeting in Paris, France.
FA y Stroke Co
nnol
ly e
t al.
NEJ
M 2
009.
Mah
affey
et a
l AH
A 20
10. C
onno
lly e
t al E
SC 2
010.
FDA APPROVES DABIGATRAN FOR AF
Indication Prevention of stroke and systemic embolism in patients
with nonvalvular atrial fibrillation
Dosing 150 mg BID for all patients except in renal impairment 75 mg BID if Cr Cl 15 – 30 mL/min No adjustment for hepatic impairment
Guidelines Take with or without meals Do not chew, break or open capsules
TRATAMIENTO DE LA ENFERMEDAD
TROMBOEMBÓLICA VENOSA
NUEVAS DROGAS
ESTUDIOS CLÍNICOS
DROGA
PREVEN.
STROKE FA
ETV y PREV TRATAMIENTO
PROFILAXIS CIRUGIA ORTOPÉDICA MAYOR
DABIGATRAN
I. DE LA TROMB
RELY RECOVER
REMEDY
RE-MOBILIZE
RE-MODEL
RE-NOVATE
RIVAROXABAN
INHIBIDOR FXa
ROCKET AF EINSTEIN PE
EINSTEIN DVT
EINSTEIN-EXT
MAGELLAN
RECORD 1
RECORD 2
RECORD 3
RECORD 4
APIXABAN
INHIBIDOR FACTOR Xa
AVERROES (ASA)
ARISTOTLE (W)
AMPLIFY
AMPLIFY-EXT
ADVANCE 1
ADVANCE 2
ADVANCE 3
Routine therapy with UFH or
LMWH
Warfarin INR 2.0 – 3.0 x 6 months
Dabigatran 150 mg BID x 6 months
Routine therapy with UFH or
LMWH
Follow-up 1
month
Follow-up 1
month
Double blind
Primary Efficacy: Recurrent, symptomatic VTEPrimary Safety: Major bleeding
• 2539 patients with acute DVTor PE treated initially with UFH/LMWH for a mean of 10 days
• Randomized to dabigatran 150 mg BID vs warfarin x 6 months• Non-inferiority study
RECOVERDabigatran in VTE Treatment
Schulman et al. New Engl J Med 2009.
Dx of VTE
Dabigatran is non-inferior to warfarin for prevention ofrecurrent or fatal VTE with comparable major bleeding risk (1.6% vs 1.9%)
Schulman et al. New Engl J Med 2009.
Dabigatran in VTE TreatmentRECOVER
INR in range 60%above range 19%below range 21%
P<0.001 for noninferiority
ESTUDIOS CLÍNICOS
DROGA
PREVEN.
STROKE FA
ETV y PREV TRATAMIENTO
PROFILAXIS CIRUGIA ORTOPÉDICA MAYOR
DABIGATRAN
I. DE LA TROMB
RELY RECOVER
REMEDY
RE-MOBILIZE
RE-MODEL
RE-NOVATE
RIVAROXABAN
INHIBIDOR FXa
ROCKET AF EINSTEIN PE
EINSTEIN DVT
EINSTEIN-EXT
MAGELLAN
RECORD 1
RECORD 2
RECORD 3
RECORD 4
APIXABAN
INHIBIDOR FACTOR Xa
AVERROES (ASA)
ARISTOTLE (W)
AMPLIFY
AMPLIFY-EXT
ADVANCE 1
ADVANCE 2
ADVANCE 3
Dx of DVT
Enoxaparin 1 mg/kd BID > 5 d, then warfarin with INR 2 – 3 x 3, 6 or 12 months (1,718)
Rivaroxaban, 15 mg BID x 21 days then 20 mg QD x 3, 6 or 12 months (1,731)
Primary Efficacy: Recurrent, symptomatic VTEPrimary Safety: Major bleeding
• 3,449 patients with acute DVT• Randomized to rivaroxaban or enoxaparin/warfarin for 3 to 12 months• Non-inferiority study
Rivaroxaban in DVT TreatmentEINSTEIN
OpenLabel
Buller et al. ASH 2010 Abstract #187. New Engl J Med 2010.
Cum
ulati
ve e
vent
rate
(%)
0 30 60 90 120 150 180 210 240 270 300 330 3600
1.0
2.0
3.0
Rivaroxaban (2.1%; 36/1,731)
Enoxaparin/VKA (3.0%; 51/1,718)4.0
Time to event (days)
Rivaroxaban in DVT TreatmentEINSTEIN
Buller et al. ASH 2010 Abstract #187. New Engl J Med 2010.
INR in range 58%above range 16% below range 24%
Rivaroxaban is non-inferior to warfarin for prevention ofrecurrent or fatal VTE with comparable major bleeding risk (0.8% vs 1.2%)
P<0.001 for noninferiority
ESTUDIOS CLÍNICOS
DROGA
PREVEN.
STROKE FA
ETV y PREV TRATAMIENTO
PROFILAXIS CIRUGIA ORTOPÉDICA MAYOR
DABIGATRAN
I. DE LA TROMB
RELY RECOVER
REMEDY
RE-MOBILIZE
RE-MODEL
RE-NOVATE
RIVAROXABAN
INHIBIDOR FXa
ROCKET AF EINSTEIN PE
EINSTEIN DVT
EINSTEIN-EXT
MAGELLAN
RECORD 1
RECORD 2
RECORD 3
RECORD 4
APIXABAN
INHIBIDOR FACTOR Xa
AVERROES (ASA)
ARISTOTLE (W)
AMPLIFY
AMPLIFY-EXT
ADVANCE 1
ADVANCE 2
ADVANCE 3
Dx of VTE and treatment for 6 – 12 months(routine Rx or rivaroxaban)
Placebo x 6 – 12 months(mean duration 190 d)
Rivaroxaban 20 mg QD x 6 – 12 months (mean duration 190 d)
Primary Efficacy: Recurrent, symptomatic VTEPrimary Safety: Major bleeding
• 1197 patients with acute DVT treated for 6 – 12 months with standard Rx or rivaroxaban
• Randomized to rivaroxaban 20 mg QD vs placebo x 6 – 12 months• Superiority Study
Rivaroxaban in Extended TreatmentEINSTEIN EXT
Buller et al. ASH 2010 Abstract #187. New Engl J Med 2010.
Double blind
1110
5
21
Cum
ulati
ve e
vent
rate
(%)
34
9
13
678
12
00 30 60 90 120 150 180 210 240 270 300 330 360
Time to event (days)
Number needed to treat to prevent 1 primary efficacy outcome: 15
HR=0.18; p<0.0001
Placebo (7.1%; 42/594)
Rivaroxaban (1.3%; 8/602)
Rivaroxaban in Extended TreatmentEINSTEIN EXT
Buller et al. ASH 2010 Abstract #187. New Engl J Med 2010.
Rivaroxaban is superior to placebo for prevention ofrecurrent or fatal VTE with comparable bleeding risk (0.7% vs 0%)
Dabigatran Can replace warfarin for treatment of acute PE/DVT
without need for monitoring Does not eliminate the need for initial UFH/LMWH Comparable to warfarin in major bleeding risk
Rivaroxaban Can replace heparin/warfarin for treatment of acute
DVT without need for monitoring Effective in reducing recurrent VTE up to 1 yr Comparable to warfarin in major bleeding risk
Studies of other agents are pending None of the new agents have received regulatory
approval for this indication to date
Treatment of Acute VTE Summary
ESTUDIOS CLÍNICOS
DROGA
PREVEN.
STROKE FA
ETV y PREV TRATAMIENTO
PROFILAXIS CIRUGIA ORTOPÉDICA MAYOR
DABIGATRAN
I. DE LA TROMB
RELY RECOVER
REMEDY
RE-MOBILIZE
RE-MODEL
RE-NOVATE
RIVAROXABAN
INHIBIDOR FXa
ROCKET AF EINSTEIN PE
EINSTEIN DVT
EINSTEIN-EXT
MAGELLAN
RECORD 1
RECORD 2
RECORD 3
RECORD 4
APIXABAN
INHIBIDOR FACTOR Xa
AVERROES (ASA)
ARISTOTLE (W)
AMPLIFY
AMPLIFY-EXT
ADVANCE 1
ADVANCE 2
ADVANCE 3
ESTUDIO MAGELLAN
OutcomeRivaroxaban, n=3997
Enoxaparin, n=4001 (%)
(%)
Clinically relevant bleeding* 2.8 1.2
Major bleeding 0.6 0.3
Fall in hemoglobin >2g/dL 0.4 0.2
Transfusions >2 units blood 0.4 0.1
Critical site bleeding 0.1 0.1
Fatal bleeding 0.1 <0.1
MAGELLAN
HR=2.3; p<0.0001
Bleeding Results at Days 1–10
Outcome Rivaroxaban, n=2967 (%)
Enoxaparin, n=3057 (%)
Composite efficacy outcome*
4.4 5.7
Asymptomatic proximal DVT
3.5 4.4
Symptomatic lower extremity DVT
0.4 0.5
Symptomatic nonfatal PE
0.3 0.5
VTE-related death 0.6 1
HR=0.77 (95% CI 0.62–0.96); p=0.02
Primary Efficacy Outcome at Day 35 MAGELLAN
Outcome Rivaroxaban, n=2939 (%)
Enoxaparin, 2993 (%)
Composite efficacy outcome*
2.7 2.7
Asymptomatic proximal DVT
2.4 2.4
Symptomatic lower extremity DVT
0.2 0.2
Symptomatic nonfatal PE
0.2 0.1
VTE-related death 0.1 0.2
Primary Efficacy Outcome at Day 10
*p for noninferiority=0.0025
MAGELLAN
Outcome Rivaroxaban, n=3997 (%)
Enoxaparin, n=4001 (%)
Clinically relevant bleeding*
1.4 0.5
Major bleeding 0.5 0.1
Fall in hemoglobin >2g/dL
0.4 <0.1
Transfusions >2 units blood
0.2 <0.1
Critical site bleeding 0.1 <0.1
Fatal bleeding <0.1 0
Bleeding Results at Days 11–35 MAGELLAN
HR=3.0; p<0.0001
RESULTADOS ESTUDIO MAGELLAN(prevencion de le etv en pacientes internados por cuadros médicos agudos)
Rivaroxaban, No inferior a la Enoxaparina a los 10 días de internación.
Superior al placebo a los 35 días.Nivel de sangrado superior a la
enoxaparina no aceptable.
Dr Alexander Cohen (King's College, London, UK) American College of Cardiology 2011 Scientific Sessions,