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Polimorfismo del citocromo P450 2C19 en pacientes jóvenes tratados con clopidogrel después de un infarto de
Jean-Philippe Collet1, Jean-Sébastien Hulot, Anna Pena
1Institut de Cardiologie, INSERM 856, Université Paris 6, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
Lancet (London, England)
|December 26, 2008
Resumen
La variante genética CYP2C19*2 aumenta significativamente el riesgo de eventos cardiovasculares adversos, incluida la trombosis de stent, en pacientes jóvenes tratados con clopidogrel después de un infarto de miocardio.
Área de la Ciencia:
- La farmacogenómica es la farmacogenómica.
- Medicina Cardiovascular La medicina cardiovascular es una especialidad de la salud.
- Genética Clínica Genética clínica.
Sus antecedentes:
- El clopidogrel y la aspirina son terapias antiplaquetarias estándar después de los síndromes coronarios agudos.
- La variante genética CYP2C19*2 tiene un impacto significativo en la eficacia antiplaquetaria del clopidogrel.
- La variabilidad individual en la respuesta al clopidogrel requiere comprender las influencias genéticas.
Objetivo del estudio:
- Para investigar el impacto pronóstico a largo plazo del polimorfismo CYP2C19*2 en jóvenes sobrevivientes de infarto de miocardio tratados con clopidogrel.
- Para determinar si el estado de portador de CYP2C19*2 influye en el riesgo de eventos isquémicos recurrentes y trombosis de stent.
Principales métodos:
- Un registro multicéntrico incluyó a 259 pacientes jóvenes (<45 años) que sobrevivieron a un primer infarto de miocardio y fueron tratados con clopidogrel.
- Se realizó la genotipización de CYP2C19*2 y los pacientes fueron seguidos durante al menos un mes.
- El criterio de valoración primario: compuesto de muerte, infarto de miocardio, revascularización urgente; el criterio de valoración secundario: trombosis de stent.
Principales resultados:
- Los portadores de CYP2C19*2 (n=73) experimentaron una mayor frecuencia del objetivo primario en comparación con los no portadores (n=186) (HR 3.69, p=0.0005).
- La trombosis del stent también fue significativamente más frecuente en los portadores (HR 6.02, p=0.0009).
- La variante CYP2C19*2 se mantuvo como un predictor independiente de eventos cardiovasculares (HR 4.04, p=0.0006) durante todo el seguimiento.
Conclusiones:
- La variante genética CYP2C19*2 es un determinante crítico del pronóstico a largo plazo en pacientes jóvenes que reciben clopidogrel después de un infarto de miocardio.
- Las pruebas genéticas para el CYP2C19*2 pueden ayudar a personalizar la terapia antiplaquetaria para optimizar los resultados.
- Comprender los perfiles farmacogenéticos puede mejorar las estrategias de prevención de eventos cardiovasculares recurrentes.
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