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Impacto del genotipo ADCY9 en la respuesta al anacetrapib
Jemma C Hopewell1, Maysson Ibrahim1, Michael Hill1,2
1Clinical Trial Service Unit and Epidemiological Studies Unit (J.C.H., M.I., M.H., L.B., M.J.L., R.C.), Nuffield Department of Population Health, University of Oxford, United Kingdom.
Circulation
|July 24, 2019
Resumen
Este estudio no encontró diferencias significativas en la eficacia del inhibidor de la proteína de transferencia de éster de colesterol (CETP) anacetrapib basado en el genotipo ADCY9 en pacientes con enfermedad vascular aterosclerótica. El genotipo ADCY9 no parece tener un impacto sustancial sobre el anacetrapib.
Área de la Ciencia:
- Medicina cardiovascular
- Farmacogenética
- La genética
Sus antecedentes:
- Los análisis exploratorios sugirieron un vínculo entre el genotipo ADCY9 y la respuesta al tratamiento con inhibidores de la proteína de transferencia de ésteres de colesterol (CETP).
- El ensayo REVEAL demostró previamente la eficacia clínica del inhibidor de la CETP anacetrapib en pacientes con enfermedad vascular aterosclerótica.
Objetivo del estudio:
- Investigar el impacto del genotipo ADCY9 en la respuesta al anacetrapib en el ensayo REVEAL.
- Determinar si el genotipo ADCY9 influye en la eficacia clínica de anacetrapib en pacientes con enfermedad vascular aterosclerótica.
Principales métodos:
- En el ensayo REVEAL se utilizó un diseño aleatorizado controlado con placebo.
- Los participantes con enfermedad vascular aterosclerótica estable recibieron anacetrapib o placebo junto con el tratamiento intensivo con atorvastatina.
- Los modelos de riesgos proporcionales de Cox analizaron los efectos de la asignación de anacetrapib y su interacción con el genotipo ADCY9 rs1967309 en eventos vasculares importantes.
Principales resultados:
- No se observaron diferencias significativas en la reducción proporcional de los eventos vasculares mayores con anacetrapib entre los diferentes genotipos de ADCY9 (GG, AG, AA).
- El valor P genotípico para la interacción fue de 0,96, lo que indica que no hay efecto farmacogenético estadísticamente significativo.
- No se encontraron asociaciones entre el genotipo ADCY9 y las reducciones en los componentes de eventos vasculares específicos o en la respuesta lipídica al anacetrapib.
Conclusiones:
- El ensayo REVEAL, el estudio más grande hasta la fecha sobre esta interacción farmacogenética, no apoya la hipótesis de que el genotipo ADCY9 sea relevante para los efectos clínicos de anacetrapib.
- Se necesitan más investigaciones, como el estudio de dal-GenE en curso, para confirmar las posibles interacciones farmacogenéticas con otros inhibidores de la CETP como el dalcetrapib.
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