Comparison of signal detection between statin and statin/ezetimibe fixed-dose combination using the Korea Adverse Events Reporting System Database, 2005-2016

Background and objectives: Statin/ezetimibe fixed-dose combination is often used as statin monotherapy; however, no study has analyzed its adverse effect (AE) signals. We comparatively analyzed the AE status of statin and statin/ezetimibe fixed-dose combination and compared the signal information using a 12-year AE reporting database. Materials and methods: We used data from the Korea Adverse Events Reporting System database from 2005 to 2016. Drug-AE pairs corresponded to drugs and AEs for analysis of demographic characteristics, causality, number, and type of serious AEs. Metrics, including proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) were used to detect signals. Signals were compared with drug labels in the USA and Korea. Results: Of the 4,569 AE cases identified, 4,130 and 442 were of statin and statin/ezetimibe fixed-dose combination, respectively. There were no statistically significant differences in AE report characterization for statin and the statin/ezetimibe fixed-dose combination. The number of AE signal detections for statin, statin/ezetimibe fixed-dose combination, and both, based on PRR and ROR, was 16, 4, and 2, respectively, and the number of cases not included on the label was 3, 2, and 0, respectively. The number of AE signals that only met IC indicators was greater in statin/ezetimibe fixed-dose combination (33) than in statin (4), and 12 of the 33 cases in statin/ezetimibe fixed-dose combination were not included on the drug label. Conclusion: The combination of statin and ezetimibe exhibited greater AE signal detection than statin alone, and the inclusion of AEs on the drug label was insufficient.