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Interacciones farmacogenéticas entre la terapia con bloqueadores beta y el polimorfismo de deleción de la enzima
D M McNamara1, R Holubkov, K Janosko
1Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. mcnamaradm@msx.upmc.edu
Circulation
|March 29, 2001
Resumen
El alelo ACE D está relacionado con una peor supervivencia a la insuficiencia cardíaca, especialmente sin terapia con beta-bloqueantes. Los betabloqueantes pueden mitigar el impacto negativo del alelo ACE D en los resultados de los pacientes.
Área de la Ciencia:
- Cardiología Cardiología.
- Farmacogenética La farmacogenética.
- Genética La genética.
Sus antecedentes:
- La renina-angiotensina y la activación del sistema nervioso simpático tienen un impacto negativo en la progresión de la insuficiencia cardíaca.
- La deleción del alelo (D) de la enzima de conversión de la angiotensina (ACE) está asociada con un aumento de la activación del sistema renina-angiotensina.
- No se comprende bien el impacto del alelo ACE D en los resultados de los pacientes y su interacción con la terapia de beta-bloqueantes.
Objetivo del estudio:
- Investigar la asociación entre el alelo ACE D y la supervivencia libre de trasplante en pacientes con disfunción sistólica.
- Evaluar la posible interacción farmacogenética entre el genotipo ACE y la terapia con beta-bloqueantes en pacientes con insuficiencia cardíaca.
Principales métodos:
- Prospectivo de seguimiento de 328 pacientes con disfunción sistólica.
- Evaluación de la supervivencia libre de trasplante basada en el polimorfismo ACE D/I (genotipos II, ID, DD).
- Comparación de las tasas de supervivencia entre pacientes con y sin terapia con beta-bloqueantes estratificados por genotipo ACE.
Principales resultados:
- Los pacientes con el alelo ACE D presentaron una supervivencia libre de trasplante significativamente peor (P = 0,044).
- El efecto adverso del alelo ACE D fue pronunciado en pacientes que no recibieron betabloqueantes (P=0,005).
- No se observó una influencia significativa del genotipo ACE en la supervivencia en pacientes tratados con betabloqueantes (P=0,73).
Conclusiones:
- El alelo ACE D se asocia con una reducción de la supervivencia libre de trasplante en pacientes con disfunción sistólica.
- Esta asociación es impulsada principalmente por pacientes que no reciben terapia con beta-bloqueantes.
- Los hallazgos sugieren una interacción farmacogenética entre el polimorfismo ACE D / I y la terapia con beta-bloqueantes en el manejo de la insuficiencia cardíaca.
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