Safety of direct oral anticoagulants: insights from postmarketing studies

Direct oral anticoagulants (DOACs) have been marketed in the United States since 2010. While numerous large-scale prospective phase 3 outcomes studies have documented the effectiveness of DOACs for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, the primary safety concern with all of these drugs-as it is with the more established oral anticoagulant warfarin-is the risk of major bleeding. Postmarketing surveillance studies (PMSS) provide the opportunity to evaluate the safety of these recently approved drugs across a spectrum of patients that may be broader than those included in randomized controlled trials. This review will summarize the safety findings of numerous recently performed, large-scale PMSS evaluations, and consider the currently available evidence regarding the risks for bleeding in patients treated with DOACs, in order to give providers and patients additional evidence regarding the safety of DOACs.