Evaluation of adverse events involving bleeding associated with oral P2Y12 inhibitors use in the Food and Drug Administration adverse event reporting system

Introduction: P2Y12 inhibitors show different bleeding-related safety profiles in premarketing trials. However, little is known about their potential safety from spontaneous reporting systems and postmarketing data. Objective: To describe and evaluate the bleeding-related adverse events associated with use of P2Y12 inhibitors utilizing data from the FDA Adverse Event Reporting System (FAERS) database. Materials and methods: We identified adverse events reports listing clopidogrel, prasugrel, or ticagrelor as the primary suspected agent in the FAERS database from the 1st quarter of 2014 to the 4th quarter of 2016. Using MedDRA version 20.0, we identified search terms for bleeding-related adverse events, within which we filtered for gastrointestinal bleeding and intracranial bleeding. Results: We identified 2,252, 2,450, and 549 adverse event reports attributed to clopidogrel, ticagrelor, and prasugrel use, respectively. Prasugrel had the highest proportional reporting ratio (PRR) (4.63; 95% confidence intervals (CI): 4.21 – 5.10) and reporting odds ratio (ROR) (7.46, 95% CI: 6.30 – 8.83) for bleeding followed by clopidogrel (PRR: 4.56; 95% CI: 4.34 – 4.78; ROR: 7.21; 95% CI: 6.63 – 7.84) and ticagrelor (PRR: 2.79; 95%CI: 2.61 – 2.98; ROR: 3.42; 95% CI: 3.12 – 3.74). Within intracranial bleeding events, both ticagrelor and prasugrel had a similarly higher incidence of fatal events than clopidogrel. Meanwhile, the incidence of gastrointestinal bleeding events leading to hospitalization was highest with clopidogrel. Conclusion: Reports on bleeding differed among P2Y12 inhibitors with respect to type and outcome. Although FAERS is subject to significant limitations, our results show that the safety profiles of P2Y12 inhibitors in the spontaneous reporting system did not differ from the results of premarketing studies.