# Small Interfering RNA for LDL-Cholesterol Reduction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Article · Batista F, Mamede I, Dacoregio M

- Archive id: doi:10.1016/j.jacadv.2026.102932
- Published: 2026-07-01
- Venue: JACC. Advances
- DOI: https://doi.org/10.1016/j.jacadv.2026.102932
- PMID: 42489386
- PMCID: PMC13400103
- Citations: 0
- Source URL: https://doi.org/10.1016/j.jacadv.2026.102932
- PDF: https://europepmc.org/articles/PMC13400103/pdf
- Provenance: europepmc

## 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 2 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 2 = 95.2%; P \< 0.001). Follow-up ranged from 0.5 to 1.5 years. Significant heterogeneity was observed (I 2 = 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.).

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cardiovascular Therapeutics](https://space-kitty.com/topics/cardiovascular-innovation)

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