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Polimorfismos genéticos y eficacia del clopidogrel para el ictus isquémico agudo o el ataque isquémico transitorio:

Yuesong Pan¹, Weiqi Chen¹, Yun Xu¹

¹From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China (Y.P.); Beijing Municipal Key Laboratory of Clinical Epidemiology, China (Y.P.); Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, China (Y.X.); Department of Neurology, The People's Hospital of Deyang City, China (X.Y.); Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China (Y.H.); Department of Neurology, Xinqiao Hospital, the Third Military Medical University, Chongqing, China (Q.Y.); Department of Neurology, the Second Hospital of Tianjin Medical University, China (X.L.); The First Affiliated Hospital, Jinan University, Guangzhou, China (L.H.); and Dell Medical School, University of Texas at Austin, TX (S.C.J.).

|November 4, 2016

Resumen

Los pacientes con accidente cerebrovascular isquémico o AIT portadores de alelos de pérdida de función del CYP2C19 se enfrentan a un mayor riesgo de accidente cerebrovascular y eventos vasculares cuando son tratados con clopidogrel. Este factor genético afecta la eficacia del clopidogrel, lo que pone de relieve la necesidad de estrategias de tratamiento personalizadas.

Área de la Ciencia:

Farmacogenómica
Neurología
Medicina cardiovascular

Sus antecedentes:

La eficacia de clopidogrel en pacientes con ictus isquémico o ataque isquémico transitorio (IAT) está influenciada por variaciones genéticas, pero los hallazgos siguen siendo inconsistentes.
El genotipo CYP2C19 es un factor genético clave investigado por su impacto en la respuesta al clopidogrel.

Objetivo del estudio:

Realizar una revisión sistemática y un metanálisis para evaluar la asociación entre los polimorfismos genéticos, en particular el genotipo CYP2C19, y la eficacia del clopidogrel en pacientes con accidente cerebrovascular o AIT.
Evaluar el riesgo de eventos clínicos, incluidos accidentes cerebrovasculares, eventos vasculares compuestos y hemorragias, basándose en perfiles genéticos.

Principales métodos:

Se realizó una búsqueda exhaustiva de literatura en PubMed y EMBASE hasta el 24 de junio de 2016.
Los estudios incluidos se centraron en pacientes tratados con clopidogrel con accidente cerebrovascular o AIT y se informaron datos de polimorfismo genético.
Los parámetros de valoración primarios fueron accidente cerebrovascular, eventos vasculares compuestos y eventos hemorrágicos.

Principales resultados:

El análisis de 15 estudios en los que participaron 4762 pacientes reveló que los portadores de alelos de pérdida de función del CYP2C19 (*2, *3, *8) tenían un riesgo significativamente mayor de accidente cerebrovascular (12,0% frente a 5,8%; RR, 1,92; P< 0,001).
Los eventos vasculares compuestos también fueron más frecuentes en estos portadores (13,7% frente a 9,4%; RR, 1,51; P=0,01), mientras que las tasas de sangrado no diferían significativamente (2,4% frente a 3,1%; RR, 0,89; P=0,59).
No se encontró una heterogeneidad significativa en el riesgo de accidente cerebrovascular, pero sí en los eventos vasculares compuestos. Otras variantes genéticas mostraron asociaciones limitadas, excepto PON1, P2Y12 y COX-1 en un estudio.

Conclusiones:

Los pacientes con ictus isquémico o AIT que son portadores de alelos de pérdida de función del CYP2C19 tienen un mayor riesgo de sufrir ictus y eventos vasculares compuestos cuando son tratados con clopidogrel.
Estos hallazgos subrayan la importancia del genotipo CYP2C19 para predecir la respuesta al clopidogrel y guiar las decisiones terapéuticas en esta población de pacientes.

Palabras clave:

el clopidogrel El citocromo P-450 y el CYP2C19 ataque isquémico, transitorio Metanálisis el golpe

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