Although the latter have short half-lives, which suggests reversal drugs may not be needed in non-urgent situations, the lack of such antidotes is a concern in emergency situations such as life-threatening major bleeding or non-elective major surgery.
1-3 Unlike warfarin and other vitamin K antagonists, there are no specific antidotes available to reverse the anticoagulant effect of DOACs. In the past decade, the use of direct oral anticoagulants (DOACs apixaban, dabigatran, edoxaban, rivaroxaban) has been approved for a number of conditions such as the prevention of stroke in patients with non-valvular atrial fibrillation (AF) the prevention of venous thromboembolism (VTE) after hip or knee replacement surgery and the treatment of VTE, as well as the prevention of VTE recurrence. Clear guidance should be available at the time these reversal drugs are commercialized to promote their appropriate use. Additional research is also needed to determine impact on clinical practice. Preliminary data shows promising results but assessment of long-term safety and efficacy requires more research.Phase 3 trials are underway for idarucizumab and andexanet alfa.
All three antidotes were well tolerated during these studies and no pro-coagulant activity was observed. Clinical evidence to support the use of individual antidotes is currently limited to phase 1 and phase 2 trials in healthy volunteers.Aripazine is a small, synthetic molecule with potentially universal anticoagulant reversal activity. Andexanet alfa is a modified recombinant factor Xa molecule that reverses oral direct (e.g., apixaban, edoxaban, rivaroxaban) and injectable indirect (e.g., enoxaparin, fondaparinux) factor Xa inhibitors. Idarucizumab is a humanized, monoclonal, antibody fragment that reverses the direct thrombin inhibitor dabigatran.There are three intravenous antidotes currently under development for the reversal of direct oral anticoagulants.
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