Work

Small Interfering RNA for LDL-Cholesterol Reduction

Year: 2026

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: Background Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for atherosclerotic cardiovascular disease. Although statins remain first-line therapy, many patients fail to achieve guideline-recommended LDL-C targets. Inclisiran, a small interfering RNA that inhibits hepatic proprotein convertase subtilisin/kexin type 9 synthesis, has emerged as a long-acting lipid-lowering strategy. This meta-analysis evaluated the efficacy of inclisiran vs placebo in reducing LDL-C levels. Objectives The purpose of this study was to systematically evaluate the efficacy of inclisiran compared with placebo in reducing LDL-C levels across diverse patient populations by synthesizing data from randomized controlled trials and to assess the consistency of LDL-C reduction and safety outcomes in the context of background lipid-lowering therapies. Methods PubMed, Embase, and Cochrane Central were systematically searched for randomized controlled trials comparing inclisiran with placebo. The primary outcome was the mean percent change in LDL-C from baseline. A random-effects model using the generic inverse variance method was applied. Heterogeneity was quantified with the I statistic. Results Nine randomized control trials comprising 6,355 participants were included. Inclisiran produced a pooled mean LDL-C reduction of −48.77% (95% CI: −54.26 to −43.27, I = 95.2%; P < 0.001). Follow-up ranged from 0.5 to 1.5 years. Significant heterogeneity was observed (I = 95%), largely attributable to differences in background lipid-lowering therapy and treatment intensification. Conclusions Inclisiran achieves substantial reductions in LDL-C across diverse patient populations. Its twice-yearly dosing schedule and small interfering RNA mechanism of action position inclisiran as a promising long-term lipid-lowering therapy, with potential for broader implementation as clinical experience and outcomes data continue to evolve. (Small Interfering RNA Therapy for LDL-Cholesterol Reduction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials; CRD420251178991 .)

Source: JACC Advances

DOI: 10.1016/j.jacadv.2026.102932

Authors: Fellipe Batista, Isadora Mamede, Maria Dacoregio

Institutions: Federal University of São João del-Rei, Universidade de São Paulo

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,936