Journal Article

The Impact of Inclisiran on Lipid Profiles in Adults with Hyperlipidemia: A Meta-Analysis and Meta-Regression of Randomized Controlled Trials

Rahman, Mohd Turzo, Khalil, Ibrahim, Hossain, Imran

2025

Overview

Hyperlipidemia is one of the most prominent risk factors for heart diseases, and current treatments are sometimes insufficient to control it. Inclisiran, a small interfering RNA targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), provides a novel, long-acting approach to improve hyperlipidemia. This meta-analysis was conducted following the PRISMA guidelines. A total of 5 out of 185 studies screened met the inclusion criteria. The primary outcome was a reduction in the LDL-C level compared to control group. Statistical analysis used a random-effect model to calculate the mean difference (MD) for with 95% confidence interval (CI). A total of 5 randomized controlled trials comprised 4,072 patients, divided into the Inclisiran arm (n = 2,129) and the Control arm (n = 1,943). Compared with control, this study showed Inclisiran substantially reduces LDL-C (MD, −51.25%; 95% CI, [−56.58 to −45.92], p <0.00001), total cholesterol (MD, −27.75%; 95% CI, [−30.39 to −25.10], p <0.00001), apolipoprotein B (MD, −36.65%; 95% CI, [−45.93 to −27.37], p = 0.00039), triglycerides (MD, −12.39%; 95% CI, [−21.49 to −3.28], p = 0.02275), PCSK9 level (MD, −77.00%; 95% CI, [−86.89 to −67.11], p = 0.00014), and lipoprotein (a) (MD, −21.77%; 95% CI, [−24.29 to −19.24], p = 0.000018). Inclisiran also significantly increases HDL-C levels by a mean difference of +5.86% (MD, 95% CI, [+4.77 to +6.95], p = 0.0001). This meta-analysis demonstrates that Inclisiran significantly improves lipid profiles in hyperlipidemia, reducing LDL-C, total cholesterol, apolipoprotein B, triglycerides, PCSK9, and lipoprotein (a), while increasing HDL-C levels. Its innovative mechanism and twice-yearly dosing enhance efficacy, safety, and patient adherence.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Apolipoprotein B / Apolipoproteins / Bias / cardiovascular risk / Cholesterol / Cholesterol, LDL - blood / Clinical outcomes / Clinical trials / Confidence intervals / Health risks / Heart diseases / High density lipoprotein / Humans / Hyperlipidemia / Hyperlipidemias - blood / Hyperlipidemias - drug therapy / Hyperlipidemias - therapy / Hypertension / inclisiran / Kexin / LDL-C reduction / lipid management / Lipids / Lipids - blood / Lipoproteins / Low density lipoprotein / Low density lipoprotein receptors / Meta-analysis / Patients / Proprotein Convertase 9 / Proprotein convertases / Randomized Controlled Trials as Topic / Regression analysis / Risk factors / siRNA / Statins / Statistical analysis / Subtilisin / Systematic review / Triglycerides / Triglycerides - blood