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Una puntuación de riesgo genético predice el riesgo de enfermedad cardiovascular e identifica a los pacientes que más se benefician de la inhibición de la PCSK9 (proprotein convertase subtilisin/kexin tipo 9). El alto riesgo genético indica un mayor beneficio del tratamiento con evolocumab.

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Área de la Ciencia:

  • Medicina cardiovascular
  • La genética
  • Farmacología

Sus antecedentes:

  • El papel de las puntuaciones de riesgo genético en la predicción del riesgo de enfermedad cardiovascular (ECV) y el beneficio del tratamiento sigue sin estar claro.
  • La estratificación del riesgo y el tratamiento personalizado de los pacientes con ECV establecidos requieren más investigación.

Objetivo del estudio:

  • Evaluar la capacidad de una puntuación de riesgo genético para predecir el riesgo en pacientes con enfermedad cardiovascular aterosclerótica establecida (ASCVD).
  • Determinar si la puntuación de riesgo genético identifica a las personas que se benefician más de la terapia de inhibición de PCSK9.

Principales métodos:

  • Análisis de 14.298 pacientes del ensayo FOURIER con VSAC.
  • Utilizó una puntuación de riesgo genético de polimorfismo de un solo nucleótido de 27 para categorizar a los pacientes en grupos de riesgo genético bajo, intermedio y alto.
  • Los factores de riesgo incluyeron diabetes, hipertensión, alto colesterol LDL y tabaquismo; múltiples factores de riesgo definieron un alto riesgo clínico.

Principales resultados:

  • La puntuación de riesgo genético predijo eventos coronarios y vasculares importantes de forma independiente (P< 0,005).
  • El alto riesgo genético se asoció con un aumento de 1,65 veces en el riesgo de eventos coronarios mayores.
  • Los pacientes con alto riesgo genético, independientemente del riesgo clínico, mostraron el mayor beneficio relativo y absoluto de evolocumab (reducción del RR del 31%, ARR del 4,0%).

Conclusiones:

  • Los pacientes sin alto riesgo genético o múltiples factores de riesgo clínico tuvieron bajas tasas de eventos y un beneficio mínimo de evolocumab.
  • El alto riesgo genético identifica a los pacientes con altas tasas de eventos que obtienen un beneficio sustancial del tratamiento con evolocumab.
  • La estratificación del riesgo genético puede personalizar las decisiones de tratamiento con inhibidores de PCSK9 en pacientes con ASCVD.