Inclisiran for LDL-C reduction in secondary prevention: Real-world evidence from a homogeneous Spanish cohort with subgroup insights

Abstract

Background

Inclisiran produces sustained LDL-C lowering in clinical trials. Real-world evidence in homogeneous secondary prevention populations is limited.

Objective

To evaluate the early effect of inclisiran on LDL-C in a homogeneous secondary prevention cohort with coronary artery disease.

Methods

We conducted a retrospective, observational study of 120 adults with established atherosclerotic cardiovascular disease treated with inclisiran between December 2023 and August 2025 at a tertiary care center in Spain. Baseline and 90-day lipid profiles were compared. Subgroup analyses examined LDL-C reduction by sex, type 2 diabetes, statin, ezetimibe, and bempedoic acid use, as well as Lp(a) and remnant cholesterol (RC) levels.

Results

Mean baseline LDL-C was 126.1 ± 34.7 mg/dL (3.26 ± 0.90 mmol/L), decreasing to 45.3 ± 28.3 mg/dL (1.17 ± 0.73 mmol/L) at 90 days (absolute change −80.9 mg/dL; −2.09 mmol/L, −63.8%). The therapeutic target, <55 mg/dL (<1.4 mmol/L), was achieved by 64.5%. Statin users had significantly greater reductions (p < 0.01). LDL-C lowering was similar across sexes despite higher baseline levels in women, and slightly greater in patients with diabetes (p = 0.48). Elevated Lp(a) showed a weak inverse correlation with LDL-C change although a trend was shown (r = −0.18). RC fell by 16.6% (p = 0.008). Bempedoic acid users (n = 16) had numerically greater reductions, though not statistically significant probably due to the low n of patients. Inclisiran was well tolerated in this cohort, with no significant adverse events reported.

Conclusions

Inclisiran achieved marked LDL-C reductions at 90 days in real-world secondary prevention, especially with the concurrent use of statins. Its twice-yearly dosing and favorable safety profile, in the term observed, support integration into guideline-directed therapy. Larger, longer-term studies should assess durability of effect, long term adherence and the impact on cardiovascular outcomes.

Resumen

Antecedentes

El inclisirán reduce de forma sostenida el c-LDL en ensayos clínicos; la evidencia en vida real en prevención secundaria homogénea es muy limitada.

Objetivo

Evaluar el efecto precoz del inclisirán sobre el c-LDL en una cohorte de prevención secundaria con enfermedad coronaria establecida.

Métodos

Estudio retrospectivo observacional en 120 adultos con ASCVD tratados con inclisirán (dic-2023–ago-2025) en un centro terciario español. Se compararon lípidos basales y a 90 días. Se analizaron los siguientes subgrupos: sexo, DM2, estatinas, ezetimiba, ácido bempedoico, Lp(a) y colesterol remanente (CR).

Resultados

bajada significativa c-LDL 126,1±34,7 a 45,3±28,3 mg/dL a 90 días (−63,8%). Objetivos: 64,5% <55 mg/dL(1,4 mmol/L). Significativamente mayor reducción con estatinas (p<0,01). Descenso similar por sexo; tendencia en DM2 (p=0,48). Lp(a) mostró correlación inversa débil a débil (r=−0,18). El CR bajó 16,6% (p=0,008). Ácido bempedoico (n=16): mayor reducción numérica sin significación estadistica por n reducido. No hubo efectos adversos relevantes.

Conclusiones

En vida real, el inclisirán logró una reducción marcada del c-LDL a 90 días, especialmente combinandolo con estatinas. Su dosificación semestral y buen perfil de seguridad apoyan su uso según las guías; se requieren estudios más amplios y prolongados para confirmar durabilidad, adherencia a largo plazo y impacto en eventos CV futuros.