Comparative Effectiveness of Inclisiran 100, 300, and 500 mg in a Population with Hyperlipidemia: A Network...

To our knowledge, inclisiran was the first agent composed of small interfering RNAs (siRNAs) to be preliminarily used to reduce proatherogenic lipoprotein cholesterol levels. Inclisiran was evaluated in large clinical trials but did not receive government approval. The ability of inclisiran to reduce low-density lipoprotein cholesterol (LDL-C) greatly improved its chances of becoming a novel therapeutic option for patients with hyperlipidemia.

Our goal was to summarize the preliminary effectiveness and safety data for inclisiran.

We conducted a comprehensive search of PubMed, Scopus, Web of Science, the OVID EMB Reviews database, and Clinical Trials with the keyword "inclisiran" to find all related randomized controlled trials (RCTs). Five recently published RCTs involving 583 adults aged 18-65 years with hyperlipidemia were included in the analysis.

Subgroup analysis suggested that inclisiran 100 mg (standard mean difference [SMD] - 2.09; 95% confidence interval [CI] - 2.51 to - 1.66; p < 0.05), 300 mg (SMD - 2.74; 95% CI - 3.61 to - 1.87; p < 0.05), and 500 mg (SMD - 2.21; 95% CI - 2.62 to - 1.80; p < 0.05) significantly (p < 0.05) reduced LDL-C and total cholesterol even though pooled analysis showed no LDL-C-lowering effect (SMD 0.15; 95% CI - 0.34 to 0.04; p = 0.116). Compared with patients receiving placebo, pooled and subgroup analysis of patients receiving inclisiran showed no favorable changes in triglycerides or high-density lipoprotein cholesterol (p > 0.05). The most commonly reported adverse events were musculoskeletal pain, nasopharyngitis, headache, and elevated C-reactive protein (CRP), none of which were significant (p > 0.05).

To date, inclisiran has been effective in treating hyperlipidemia. Major adverse events were not identified, although other possible adverse events may be discovered with more RCTs and extensive long-term follow-up.