Reversal agents for current and forthcoming direct oral anticoagulants

Eur Heart J. 2023 May 21;44(20):1795-1806. doi: 10.1093/eurheartj/ehad123.

Abstract

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.

Keywords: Andexanet; DOACs; Direct oral anticoagulants; Factor XI inhibitors; Idarucizumab.

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / adverse effects
  • Dabigatran* / adverse effects
  • Factor Xa Inhibitors / pharmacology
  • Factor Xa Inhibitors / therapeutic use
  • Hemorrhage / chemically induced
  • Hemorrhage / prevention & control
  • Humans
  • Recombinant Proteins / therapeutic use
  • Rivaroxaban* / therapeutic use
  • Vitamin K

Substances

  • edoxaban
  • Dabigatran
  • Rivaroxaban
  • Anticoagulants
  • Factor Xa Inhibitors
  • Recombinant Proteins
  • Vitamin K