Assessing the Impact of Inclisiran on LDL-C and PCSK9 Reduction in Hypercholesterolemic Patients: A Meta-analysis of Cardiovascular Metabolic Prevention

Hypercholesterolemia, a major contributor to atherosclerotic cardiovascular disease, remains inadequately controlled despite widespread statin use, particularly in patients with familial hypercholesterolemia or statin intolerance. Inclisiran, a novel small interfering RNA therapeutic, targets hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis to provide sustained low-density lipoprotein cholesterol (LDL-C) reduction. This meta-analysis evaluated the efficacy of inclisiran 300 mg in lowering LDL-C and PCSK9 levels in patients with general hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). A systematic search of PubMed, Cochrane, Wiley, and Scopus up to July 2025 identified 11 randomized controlled trials comparing inclisiran 300 mg with placebo. Pooled results showed significant LDL-C reductions of -31.89 mg/dL for general hypercholesterolemia and -61.47 mg/dL for HeFH; PCSK9 decreased by -65.96 ng/mL and -56.41 ng/mL, respectively, with no significant subgroup differences observed. Although the risk of bias was low, heterogeneity (I² >50%) and mild funnel plot asymmetry indicated potential variability and small-study effects. Overall, Inclisiran demonstrates consistent and substantial lipid-lowering efficacy across diverse hypercholesterolemic populations, supporting its use as an adjunct or alternative to statins. Its twice-yearly dosing may offer benefits for adherence and long-term lipid control; however, further studies are needed to confirm benefits on cardiovascular outcomes.