Aspirin- and Clopidogrel-associated Bleeding Complications: Data Mining of the Public Version of the FDA Adverse Event Reporting System, AERS

OBJECTIVE Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the bleeding complications induced by the administration of antiplatelets and to attempt to determine the rank-order of the association. METHODS After a deletion of duplicated submissions and the revision of arbitrary drug names, AERs involving warfarin, aspirin, cilostazol, clopidogrel, ethyl icosapentate, limaprost alfadex, sarpogrelate, and ticlopidine were analyzed. Authorized pharmacovigilance tools were used for the quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. RESULTS Based on 22,017,956 co-occurrences, i.e., drug-adverse event pairs, found in 1,644,220 AERs from 2004 to 2009, 736 adverse events were listed as warfarin-associated adverse events, and 147 of the 736 were bleeding complications, including haemorrhage and haematoma. Both aspirin and clopidogrel were associated with haemorrhage, but the association was more noteworthy for clopidogrel. As for bleeding complications related to the gastrointestinal system, e.g., melaena and haematochezia, the statistical metrics suggested a stronger association for aspirin than clopidogrel. The total number of co-occurrences was not large enough to compare the association with bleeding complications for the other 5 antiplatelets. CONCLUSIONS The data strongly suggest the necessity of well-organized clinical studies with respect to antiplatelet-associated bleeding complications.