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Efecto de la inhibición de PCSK9 con alirocumab en pacientes con probable hipercolesterolemia familiar o

Gregory P Geba¹, Kusha A Mohammadi¹, Amy Damask¹

¹Regeneron Pharmaceuticals, Inc. Tarrytown NY USA.

Journal of the American Heart Association

|August 23, 2025

Resumen

Alirocumab trató eficazmente a pacientes con hipercolesterolemia familiar heterocigótica (HEF) y hiperlipoproteinemia tipo III (T3HLP), mostrando respuestas lipídicas y beneficios clínicos similares en todos los grupos. Ambas afecciones, aunque con una prevalencia diferente, respondieron bien al tratamiento con alirocumab.

Palabras clave:

El LDL-C el alirocumab Hipercolesterolemia heterocigótica y familiar hiperlipoproteinemia de tipo III

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Área de la Ciencia:

Medicina cardiovascular
La genética
Farmacología

Sus antecedentes:

El ensayo ODYSSEY OUTCOMES evaluó la eficacia de alirocumab después del síndrome coronario agudo.
Este análisis se centró en pacientes con probable hipercolesterolemia familiar heterocigótica (HEF) o hiperlipoproteinemia tipo III (T3HLP).

Objetivo del estudio:

Evaluar la eficacia de alirocumab en pacientes con HEF y PHLT.
Analizar las respuestas lipídicas y los resultados clínicos en estos subgrupos específicos de pacientes.

Principales métodos:

HeFH clínica definida en función de los niveles de colesterol LDL y el momento en que ocurre.
T3HLP identificado utilizando la relación colesterol no HDL/ApoB y validado con datos del Biobanco del Reino Unido.
Variaciones genéticas evaluadas (HeFH) y genotipos APOE (T3HLP) en un subgrupo farmacogenómico.

Principales resultados:

El 5,8% de los pacientes de ODYSSEY OUTCOMES tenía HEF clínica; el 2,5% tenía HEF genéticamente confirmada.
Alirocumab mostró respuestas lipídicas y beneficios clínicos similares en pacientes con o sin HEF.
El 0,16% de los pacientes tenían T3HLP, siendo el 53,8% homocigotos APOE2/ 2; las respuestas lipídicas fueron comparables a la población general.
La incidencia de eventos adversos fue similar en los subgrupos de dislipidemia genética y en la cohorte general.

Conclusiones:

HeFH fue común, mientras que T3HLP fue raro en el ensayo ODYSSEY OUTCOMES.
Los pacientes con HeFH y T3HLP demostraron respuestas lipídicas beneficiosas a alirocumab.
Alirocumab es eficaz para el control de los lípidos en pacientes con estas dislipidemias genéticas.