Muscle Adverse Events Associated with Inclisiran: Data Mining of FAERS database and Mendelian Randomization Analysis

J Cardiovasc Pharmacol. 2025 Nov 25. doi: 10.1097/FJC.0000000000001778. Online ahead of print.

ABSTRACT

Inclisiran, the first small interfering RNA (siRNA) lipid lowering drug, has reported muscle adverse events (MAEs), but long-term safety is unclear. This study is based on data obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, covering the period from December 22, 2021, to December 31, 2024. MAEs signals of Inclisiran were mined by calculating reporting odds ratios (ROR) and the Bayesian confidence propagation neural network (BCPNN). Stratification analysis, serious and non-serious cases were compared, and signals were prioritized using a rating scale. Additionally, we employed mendelian randomization (MR) to investigate the causal relationship between Inclisiran and musculoskeletal system diseases. Among 4,685 adverse event reports of Inclisiran, 523 MAEs reports were found. Inclisiran has potential signals in terms of MAEs (ROR:7.51, 95%CI:6.86-8.23; IC:2.75, IC025:2.60). Inclisiran-related MAEs signal intensity was lower compared to statins (ROR:0.40, 95%CI:0.37-0.44), but higher than other PCSK9 inhibitors (ROR:5.85, 95%CI:5.26-6.50). Combination with statins/fibrates rarely increased MAE risk or signal strength. Notably, the signal between Inclisiran and MAEs can still be detected when stratified by gender, age, reporter type and serious report. Among the 7 PTs identified, muscle spasms and myalgia are of moderate clinical priority signals and should be given particular attention. MR analysis further validated that Inclisiran may be potentially associated with an increased risk of musculoskeletal system diseases. This study revealed that MAEs associated with Inclisiran. Additional laboratory and clinical monitoring should be considered for patients taking Inclisiran for timely diagnosis and management of MAEs.

PMID:41289434 | DOI:10.1097/FJC.0000000000001778