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.
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