Abstract
The advent of direct-acting oral anticoagulants (DOACs) has transformed the care of patients requiring prevention and treatment for thrombotic disease. Many randomized clinical trials have demonstrated the efficacy and safety of these agents and their comparative advantages over conventional anticoagulants such as vitamin K antagonists (VKAs). While historically clinicians and patients raised questions about the reversal of DOAC-associated bleeding, federal approval in recent years of targeted DOAC reversal agents, along with adjunctive modalities, has given clinicians reliable pharmacologic options. Yet, optimal reversal strategies for bleeding at specific anatomic locations and in specific clinical scenarios remains uncertain. We present here a narrative review of the literature on the reversal of DOAC-associated bleeding or for urgent procedures. The totality of the reversal literature synthesized here yields several clear conclusions: (1) targeted DOAC reversal with specific agents demonstrates superior efficacy for both bleeding and urgent surgical indications when compared to the use of non-specific agents, such as prothrombin complex concentrates (PCCs); (2) at the same time, high-quality data suggest potentially increased thrombotic risks, particularly for ischemic stroke, when using the specific targeted agent andexanet; (3) in all cases of life-threatening bleeding, timely reversal is of the essence; (4) in particular, there is growing consensus that DOAC-associated intracranial hemorrhage (ICH) should be reversed promptly, with a goal door-to-reversal time of 60 min; (5) future research will focus on optimizing clinical pathways for reversal to address "calls to action" from professional groups on this critical topic.