A real-world pharmacovigilance study of bempedoic acid plus ezetimibe fixed-dose combination based on the FDA FAERS...

The bempedoic acid plus ezetimibe fixed-dose combination (BAPEFC) is a novel lipid-lowering agent that was successively marketed in regions such as the United States and the European Union in 2020. It significantly reduces low-density lipoprotein cholesterol through a dual mechanism of inhibiting adenosine triphosphate-citrate lyase and Niemann-Pick C1-like 1. Although clinical trials have confirmed its efficacy, its long-term safety in the real world requires further evaluation. All adverse event reports related to BAPEFC from the first quarter of 2020 to the first quarter of 2025 were extracted from the FDA Adverse Event Reporting System (FAERS) database. After data standardization, a comprehensive evaluation of adverse reaction signals was performed using the reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. Subgroup analyses by sex and age were further conducted for newly identified adverse drug reactions. A total of 875 reports involving at least 1 BAPEFC agent were identified in FAERS. The preferred term with the highest number of reports was arthralgia (n = 103), while the strongest positive signal was for tendon discomfort (n = 3, ROR = 135.27, proportional reporting ratio = 135.03, information component = 7.06, empirical Bayes geometric mean = 133.36). At the system organ class level, musculoskeletal and connective tissue disorders had the highest ROR value (ROR = 6.02, 95% confidence interval [CI]: 5.46-6.63). The newly identified signal for "Blood Triglycerides Increased" showed statistically significant ROR signals in both male and female subgroups (ROR = 36.59 [95% CI: 15.16-88.32] vs ROR = 34.78 [95% CI: 15.57-77.67]), and the adjusted Bonferroni-P values were statistically significant (Bonferroni-P < .0001). Subgroup analysis of the combined data for the newly identified "Pancreatitis" and "Pancreatitis Acute" showed statistically significant ROR signals in both the non-elderly subgroup (<65 years) and the elderly subgroup (≥65 years) (ROR = 10.43 [95% CI: 4.32-25.18] vs ROR = 5.88 [95% CI: 2.2-15.71]), and the adjusted Bonferroni-P values were statistically significant (Bonferroni-P = .0003 vs Bonferroni-P = .0106). Based on the FAERS database, this study provides the first comprehensive and systematic analysis of adverse drug events associated with BAPEFC. It newly identifies several adverse drug reactions not mentioned in the prescribing information, such as blood triglycerides increased, pancreatitis, and pancreatitis acute, thereby offering evidence for clinical monitoring and identification of potential risks associated with BAPEFC.