Efficacy and Safety of Inclisiran, Alirocumab, Evolocumab, and Evinacumab in Lipid-Lowering: A Network Meta-Analysis

Abstract Purpose To indirectly compare the efficacy and safety of inclisiran, alirocumab, evolocumab, and evinacumab in lipid-lowering through a network meta-analysis. Methods Randomized controlled trials (RCTs) were retrieved from databases including PubMed, EMBASE, Web of Science, and Cochrane Library. The search was conducted up to July 1, 2023. The quality of included studies was assessed using the Cochrane risk of bias tool, and data analysis was performed using R software. Results A total of 21 randomized controlled trials involving 10,835 patients were included. The network meta-analysis indicated that Evolocumab was the most effective (87%) in reducing low-density lipoprotein cholesterol (LDL-C), followed by alirocumab (71.4%) and inclisiran (47.2%), with placebo being the least effective (0.01%). In increasing high-density lipoprotein cholesterol (HDL-C), evolocumab ranked first (81.8%), followed by alirocumab (68.2%), with placebo again at the bottom (0.03%). In lowering total cholesterol, evolocumab performed the best (86%), followed by alirocumab (64%), and placebo remained the least effective (0.04%). Regarding adverse events (AEs), evinacumab ranked the highest (98.9%), followed by inclisiran (59.6%) and evolocumab (15.2%). Conclusion Evolocumab appears to be the most effective in increasing HDL-C, and reducing LDL-C and total cholesterol. Evinacumab shows the best safety profile with the lowest incidence of AEs.