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 (siRNA) that inhibits hepatic PCSK9 synthesis, has emerged as a long-acting lipid-lowering strategy. This meta-analysis evaluated the efficacy of inclisiran versus placebo in reducing LDL-C levels.
Objectives: To systematically evaluate the efficacy of inclisiran compared with placebo in reducing low-density lipoprotein cholesterol (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 I² statistic.
Results: Nine RCTs comprising 6,355 participants were included. Inclisiran produced a pooled mean LDL-C reduction of -48.76% (95% CI: -53.53 to -43.99; p< 0.00001). Follow-up ranged from 0.5 to 1.5 years. Significant heterogeneity was observed (I² = 91%), largely attributable to differences in background lipid-lowering therapy and treatment intensification.
Conclusion: Inclisiran consistently achieves substantial LDL-C reductions across diverse patient populations. Its twice-yearly dosing schedule and siRNA 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. Keywords: Inclisiran, siRNA, hypercholesterolemia, LDL-C.
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