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.

Automated summary

In the past 20 years, there has been a transition from vitamin K antagonists to direct oral anticoagulants (DOACs). DOACs include dabigatran, apixaban, edoxaban, and rivaroxaban. Although DOACs are associated with less serious bleeding, reversal agents may be needed in cases of serious bleeding or urgent surgery/intervention. This paper provides insight into reversing the effects of DOACs, discusses new reversal agents, and outlines a strategic framework for reversing factor XI inhibitors in clinical trials.