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BIVALIRUDINA EN ICP:
EVIDENCIA ACTUAL
DR. JUAN CARLOS BECERRA MARTÍNEZ
SERVICIO DE HEMODINÁMICA
CENTRO MÉDICO NACIONAL DE OCCIDENTE, IMSS
GUADALAJARA, MÉXICO
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Bivalirudina:
Angiomax Costo: 400 veces mas que la heparina
Reduce isquemia similar a la HNF con menos sangrados en contexto de ICP
Se une directo a la trombina (factor IIa) e impide la conversión de fibrinógeno a fibrina
Opie, LH. Drugs for the Heart. 8th Ed. 2013
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Bivalirudina:
Opie, LH. Drugs for the Heart. 8th Ed. 2013
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Bivalirudina:
Farmacocinética: Cinética linearNo se une a proteínasPocas interacciones farmacológicasInhibe a la trombina soluble y la unida al coágulo Bloquea la activación plaquetaria mediada por
trombinaSe elimina por proteólisis (80%) y renal (20%)Niveles plasmáticos se correlacionan bien con
ACT
Opie, LH. Drugs for the Heart. 8th Ed. 2013
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Bivalirudina:
Menor sangrado:Con mismos ACT, pacientes con bivalirudina
sangran menos que con heparina +- GPI IRC (<30 ml/min):
ESC recomienda infusión 1 mg/kg/hr Licencia “on label” por FDA:
ICP planeada (sin beneficio en tx médico)Pacientes con trombocitopenia inducida por
heparina
Opie, LH. Drugs for the Heart. 8th Ed. 2013
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Bivalirudina:
ICP electiva:Bivalirudina + GPI selectiva da mismos resultados
que HNF + GPI rutinario con menos sangrado
Dosis: 0.75 mg/kg Infusión de 1.75 mg/kg/hr por lo que dure el procedimiento (o 4 hrs)○ CrCl <30 ml/min: Infusión 1 mg/kg/hr○ Hemodiálisis: Infusión 0.25 mg/kg/hr
Opie, LH. Drugs for the Heart. 8th Ed. 2013
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Bivalirudina:
SICA con ICP:ACUITY: Bivalirudina mismos resultados que
HNF+GPI con menos sangrados. Pero bivalirudina + GPI rutinario sin beneficio con MAS sangrado
JAMA. 2007;297:591-602
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Bivalirudina:
SICA con ICP:QUE MENSAJE NOS DEJA ACUITY?
JAMA. 2007;297:591-602
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Contexto clínico HORIZONS-AMI
Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction
Columbia University Medical Center, NY
N Engl J Med 2008;358:2218-30.
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Contexto clínico
HORIZONS-AMI:3,602 pacientesSICA CESST <12 hrsAleatorización:
○ Bivalirudina (Bolo 0.75 mg/kg Infusión 1.75mg/kg/hr)
○ Heparina (60 U/kg ACT 200-250 s) + Inhibidor gpIIb/IIIa
Seguimiento a 30 días
N Engl J Med 2008;358:2218-30.
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Contexto clínico
HORIZONS-AMI:
N Engl J Med 2008;358:2218-30.
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Contexto clínico
HORIZONS-AMI:Objetivo primario del estudio:
1. Sangrado mayor
2. Compuesto de eventos clínicos adversos:1. Sangrados
2. Muerte
3. Re-IAM
4. Revascularización repetida
5. EVC
N Engl J Med 2008;358:2218-30.
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Contexto clínico
Heparina + Inhib gpIIb/IIIa
Bivalirudina Valor de P
Sangrado mayor 8.4% 5.0% <0.001
Trombocitopenia 2.9% 1.1% 0.003
MACE (muerte, re-IAM, EVC, revasc repetida)
5.5% 5.4% 0.95
N Engl J Med 2008;358:2218-30.
HORIZONS-AMI:
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Contexto clínico
N Engl J Med 2008;358:2218-30.
HORIZONS-AMI:
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Contexto clínico
N Engl J Med 2008;358:2218-30.
HORIZONS-AMI:
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Contexto clínico
N Engl J Med 2008;358:2218-30.
HORIZONS-AMI:
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Contexto clínico
N Engl J Med 2008;358:2218-30.
HORIZONS-AMI:
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Contexto clínico
HORIZONS-AMI (3 AÑOS):
Lancet. 2011 Jun 25;377(9784):2193-204
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Contexto clínico
HORIZONS-AMI (3 AÑOS):
Lancet. 2011 Jun 25;377(9784):2193-204
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Contexto clínico EUROMAX
European Ambulance Acute Coronary Syndrome Angiography
Hospital Bichat, Paris
N Engl J Med 2013;369:2207-17
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Contexto clínico
EUROMAX2,218 pacientes con SICA CESST <12 hrsAleatorizados a:
○ Bivalirudina (Bolo 0.75 mg/kg Infusión 1.75mg/kg/hr)○ Control:
Heparina (60 U/kg con GPI o 100 U/kg sin GPI) Enoxaparina (0.5mg/kg IV)
Inhibidores de gpIIb/IIIa opcional (rutinario o bailout)Seguimiento a 30 díasObjetivo primario:
○ Compuesto de muerte o sangrado mayorObjetivo secundario:
○ Compuesto de muerte, re-IAM y sangrado mayorN Engl J Med 2013;369:2207-17
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Contexto clínico
N Engl J Med 2013;369:2207-17
EUROMAX
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Contexto clínico
N Engl J Med 2013;369:2207-17
EUROMAX
The routine use of a gp IIb/IIIa inhibitor in the bivalirudin group was a deviation from the protocol.
Bivalirudin Control
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Contexto clínico
N Engl J Med 2013;369:2207-17
EUROMAX
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Contexto clínico
N Engl J Med 2013;369:2207-17
EUROMAX
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Contexto clínico
N Engl J Med 2013;369:2207-17
EUROMAX
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Contexto clínico
N Engl J Med 2013;369:2207-17
EUROMAX
AMBOS OBJETIVOS A EXPENSAS DE MENOR SANGRADO
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Contexto clínico
N Engl J Med 2013;369:2207-17
EUROMAX
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HEAT-PPCI
How Effective are Antithrombotic Therapies in Primary PCI Liverpool Heart and Chest Hospital, UK
Aleatorizado, abierto, 1,812 pacientes, Seguimiento a 28 días
Objetivo 1° eficacia: muerte, EVC, re-IAM, PCI repetida Objetivo 1° seguridad: sangrado mayor (tipo 3-5 BARC)
Lancet. 2014 Jul 4
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HEAT-PPCI
Consenso que dio origen a la clasificación BARC:
Las definiciones de sangrado eran muy heterogéneas: TIMI, GUSTO, CURE, ACUITY-HORIZONS, CURRENT-
OASIS, STEEPLE, PLATO, GRACE, REPLACE-2, ESSENCE, AMLANI…
Circulation. 2011;123:2736-2747
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HEAT-PPCI
Bleeding Academic Research Consortium: Tipo 0: no sangrado Tipo 1: no requiere evaluación ni tratamiento Tipo 2: requiere evaluación y tratamiento Tipo 3:
○ 3a: Descenso de Hb 3-5 g/dL, transfusión○ 3b: Descenso de Hb >5 g/dL, tamponade, cirugía○ 3c: HIC, hemorragia retiniana
Tipo 4: sangrado por CABG Tipo 5: sangrado fatal
○ 5a: sangrado fatal por sospecha clínica○ 5b: sangrado fatal con autopsia o imagen
Circulation. 2011;123:2736-2747
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HEAT-PPCI
Aleatorización a:Heparina 70 U/kg Bivalirudina
○ Bolo 0.75 mg/kg Infusión 1.75mg/kg/hr
Inhibidores gpIIb/IIIa solo de rescateGrupo heparina: 15%Grupo bivalirudina: 13%
ICP:Grupo heparina: 82%Grupo bivalirudina: 83%
Lancet. 2014 Jul 4
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HEAT-PPCI
Lancet. 2014 Jul 4
El primer mundo…Bivalirudin (n=905) Heparin (n=907)
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HEAT-PPCI
Lancet. 2014 Jul 4
Características de los pacientes:Bivalirudin (n=905) Heparin (n=907)
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HEAT-PPCI
Lancet. 2014 Jul 4
Medicamentos al alta:Bivalirudin (n=905) Heparin (n=907)
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HEAT-PPCI
Objetivo primario de eficacia:Heparina: 5.7%Bivalirudina: 8.7% (RR 1.52, p=0.01)
Lancet. 2014 Jul 4
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HEAT-PPCI
Objetivo primario de seguridad:Heparina: 3.1%Bivalirudina: 3.5% (p=0.59)
Lancet. 2014 Jul 4
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HEAT-PPCI
Bivalirudina Heparina RR Valor p
Objetivo primario de eficacia
Muerte 5.1% 4.3% 1.18 0.43
EVC 1.6% 1.2% 1.37 0.43
Re-IAM 2.7% 0.9% 3.01 0.004
Revasc. repetida 2.7% 0.7% 4.01 0.001
Objetivo secundario de eficacia
Trombosis del stent aguda (<24 hrs)
3.4% 0.9% 3.9 0.001
Lancet. 2014 Jul 4
*Trombosis de stent subaguda (24 hrs a 1 mes) no significativa (p=0.12)
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HEAT-PPCI
Lancet. 2014 Jul 4
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Discusión La bivalirudina ofrece menor incidencia de
sangrados mayores comparado con heparina + inhibidores de gpIIb/IIIa rutinarios
No se ha demostrado que la bivalirudina disminuya eventos isquémicos comparado con heparina o HBPM; por el contrario, incrementa la incidencia de trombosis aguda de stent.
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Discusión HEAT-PPCI es el primer ensayo aleatorizado
en comparar bivalirudina y heparina con inhibidores de gpIIb/IIIa de rescate en ambos grupos
La heparina con inhibidores de gpIIb/IIIa de rescate disminuye eventos isquémicos y trombosis aguda de stent con misma incidencia de sangrado comparado con bivalirudina.
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¿Qué dicen las guías?
HORIZONS-AMI
CURRENT-OASIS 6
European Heart Journal (2012) 33, 2569–2619
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¿Qué dicen las guías?
BIVALIRUDIN DOSAGE:
• 0.75 mg/kg i.v. bolus• I.V. infusion of 1.75 mg/kg/h for up to 4 h after the procedure• A reduced infusion dose of 0.25 mg/kg/h may be continued for 4–12 h as clinically necessary.
European Heart Journal (2012) 33, 2569–2619
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¿Qué dicen las guías?
NADA
European Heart Journal (2013) 34, 2949–3003
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¿Qué dicen las guías?
ACUITYACUITYACUITY
European Heart Journal (2011) 32, 2999–3054
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¿Qué dicen las guías?
European Heart Journal (2010) 31, 2501–2555
ACUITY
ACUITY
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¿Qué dicen las guías?
European Heart Journal (2010) 31, 2501–2555
HORIZONS-AMI
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Por su atención…
Gracias!