Background: Although the use of direct oral anticoagulants (DOACs) has been reported in patients with atrial fibrillation (AF), there is currently no consensus on the occurrence or characteristics of the hemorrhage risk in different antithrombotic regimens.
Methods: Disproportionality and Bayesian analyses were performed in mining data of suspected hemorrhagic events after antithrombotic drug use from the FDA Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset and fatality rate of hemorrhage following different antithrombotic regimens were also compared.
Results: A total of 84,998 reports of hemorrhage-related adverse events with the use of antithrombotic drugs were identified. The patients included were mostly from the Americas (80.87%) and Europe (13.22%), with most data submitted by nonhealthcare professionals. Among the seven antithrombotic drug monotherapies, betrixaban had the highest association with hemorrhage based on the highest reporting odds ratio (ROR, 829.95; 95% CI = 113.61-6063.15), proportional reporting ratio (PRR, 24.68, χ2 = 804.24), and multi-item gamma Poisson shrinker (MGPS, 24.68, 95% one-sided CI = 4.67). The combination therapies of clopidogrel plus new oral anticoagulants had higher RORs, PRRs, and empirical Bayesian geometric means (EBGMs) than the antithrombotic drug monotherapies. Hemorrhage associated with rivaroxaban plus clopidogrel appeared to have an earlier onset (171 days vs 219 days, 95% two-sided CI =68.68-27.34, p < 0.0001) and a lower fatality rate (15.30% vs 17.74%, p<0.05) than that associated with rivaroxaban monotherapy.
Conclusion: This study provides a relevant overview of the hemorrhagic complications/fatalities associated with different antithrombotic regimens in their real-world use. Among the combination therapies, clopidogrel plus DOACs were found to have stronger associations with hemorrhage than traditional dual antithrombotic therapies. Rivaroxaban showed a stronger association with hemorrhage than other antithrombotic drug monotherapies, and apixaban monotherapy appeared to have weaker associations with hemorrhage than others.
Keywords: Adverse drug events; Antithrombotic; Data mining; Hemorrhage; Spontaneous reporting system.
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