Reversal agents for current and forthcoming direct oral anticoagulants.

Over the past 20 years, there has been a shift from vitamin K antagonists to direct oral anticoagulants (DOACs), which include the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban. Although DOACs are associated with less serious bleeding than vitamin K antagonists, bleeding still occurs with DOACs, particularly in the elderly and in those with comorbidities. Reversal of the anticoagulant effects of the DOACs may be needed in patients with serious bleeding and in those requiring urgent surgery or intervention. Reversal can be effected with specific agents, such as idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, or with non-specific agents, such as prothrombin complex concentrates, activated prothrombin complex concentrate, and recombinant activated factor VII. This paper (i) provides an update on when and how to reverse the DOACs, (ii) describes new reversal agents under development, and (iii) provides a strategic framework for the reversal of the factor XI inhibitors currently under investigation in phase three clinical trials.
Competing Interests: Conflict of interest J.W. has received grant funding from the Canadian Institutes of Health Research. He is a consultant for and received honoraria from Bayer, Alnylam, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer, Regeneron, and Servier. N.v.E has received grant funding from the Dutch Thrombosis Foundation. He has received honoraria from Boehringer Ingelheim. R.d.C. is a consultant for and received honoraria from Bayer, Janssen–BMS, BMS–Pfizer Alliance, Daiichi-Sankyo, Menarini, Milestone, Portola, Guidotti, Novartis, Merck, Roche, and AstraZeneca. He has participated on the Advisory Board for Janssen–BMS.
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