REVERSAL AGENTS FOR THE DIRECT ORAL ANTICOAGULANTS

In phase III clinical trials, the direct oral anticoagulants have shown a favorable safety profile in comparison to vitamin K antagonists. Yet, there is an important need for the availability of adequate emergent reversal strategies when managing patients treated with the DOACs. A number of strategies have been proposed, but are not supported by adequate evidence from clinical studies. These include the administration of activated charcoal, hemodialysis to reverse the effects of dabigatran, or the use of nonspecific reversal agents, such as prothrombin complex concentrate, activated PCC, and recombinant factor VIIa. More recently, specific reversal agents have started to become available. Idarucizumab, a monoclonal antibody fragment that directly binds to dabigatran, was licensed for clinical use in several countries worldwide; andexanet alfa, a recombinant factor Xa that binds oral direct factor Xa inhibitors, but also heparins and fondaparinux, is expected to receive approval by the Food and Drug Administration in the United States; whereas ciraparantag is in an earlier development phase. The preliminary results of phase III prospective cohort studies with idarucizumab and andexanet alfa have confirmed their ability to rapidly achieve reversal of the anticoagulant effect of dabigatran and factor Xa inhibitors, respectively. With their availability for clinical use, local protocols to define correct indications for these reversal agents are warranted.