First real-world experience with inclisiran in Spain: Efficacy, safety, and prescription patterns in clinical practice

Abstract

Background

Low-density lipoprotein cholesterol (LDL-C) is a key causal factor in atherosclerotic cardiovascular disease. Although statins remain the cornerstone of treatment, their use is limited by adverse effects, variable response and poor adherence. Inclisiran, a small interfering RNA that inhibits hepatic PCSK9 synthesis, has demonstrated marked LDL-C reductions in clinical trials. However, real-world evidence remains limited.

Methods

Observational longitudinal study in a Spanish tertiary hospital including all patients prescribed inclisiran since its approval. Baseline characteristics were analysed. LDL-C target achievement and safety outcomes were assessed.

Results

Seventy-seven patients were included (median age 59 years), most of whom were at high or very high cardiovascular risk; 82% were treated for secondary prevention and 41% had statin intolerance. Median baseline LDL-C was 115 [103–133] mg/dL. Mean LDL-C reductions were 52% at 3 months, 61% at 9 months and 52% at 15 months. Greater reductions were observed in patients receiving concomitant high-potency statins. Individualised LDL-C targets were achieved in 59%, 52% and 56% of patients at 3, 9 and 15 months, respectively. Adverse events were infrequent (5%) and limited to mild injection-site reactions. Eleven per cent of patients were lost to follow-up, mainly due to poor adherence.

Conclusions

In routine clinical practice, inclisiran was effective and well tolerated, producing substantial and sustained reductions in LDL-C in a predominantly high-cardiovascular-risk population. Its favourable safety profile and twice-yearly administration make it a practical therapeutic option, particularly for patients with statin intolerance or adherence difficulties, and support its integration into real-world care pathways.

Resumen

Antecedentes

El colesterol de lipoproteínas de baja densidad (LDL) es un factor causal clave en la enfermedad cardiovascular aterosclerótica. Aunque las estatinas siguen siendo la base del tratamiento, su uso está limitado por efectos adversos, respuesta variable y baja adherencia. Inclisiran, un pequeño ARN de interferencia que inhibe la síntesis hepática de PCSK9, ha demostrado reducciones significativas del LDL en ensayos clínicos. Sin embargo, la evidencia en la práctica clínica real sigue siendo limitada.

Métodos

Estudio observacional longitudinal en un hospital terciario español que incluyó a todos los pacientes a los que se prescribió inclisiran. Se analizaron las características basales. Se evaluó la consecución de los objetivos de LDL y los resultados de seguridad.

Resultados

Se incluyeron 77 pacientes (edad mediana de 59 años). 82% recibía tratamiento en prevención secundaria y el 41% presentaba intolerancia a estatinas. El LDL basal mediano fue de 115 [103–133] mg/dL. Las reducciones medias de LDL fueron del 52% a los 3 meses, 61% a los 9 meses y 52% a los 15 meses. Los objetivos individualizados de LDL-C se alcanzaron en el 59%, 52% y 56% de los pacientes a los 3, 9 y 15 meses, respectivamente. Los eventos adversos fueron leves y poco frecuentes (5%).

Conclusiones

En la práctica clínica habitual, inclisiran fue eficaz y bien tolerado, produciendo reducciones sustanciales y sostenidas del LDL en una población predominantemente de alto riesgo cardiovascular. Su favorable seguridad y su administración semestral lo convierten en una opción terapéutica práctica, especialmente en pacientes con intolerancia a estatinas o dificultades de adherencia.