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

Abstract

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.