Small Interfering RNA for LDL-Cholesterol Reduction

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: statistic. RESULTS: = 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.).