DIRECT ORAL ANTICOAGULANTS: NEW PERSPECTIVES ON REVERSAL AGENTS

Direct Oral Anticoagulants (DOACs) have been approved for stroke prevention in patients with atrial fibrillation (AF) and for venous thromboembolism (VTE) treatment and prevention after major orthopedic surgery. DOACs are at least as effective and have many advantages over warfarin, including the better outcomes of major bleeds and the more satisfactory safety profile. However, one of the most important drawbacks of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations. Currently, three antidotes for reversal of anticoagulant activity of DOACs are at different levels of development: Idarucizumab, the first novel antidote available in the clinical practice, against direct thrombin inhibitor dabigatran; Andexanet alfa, a specific reversal agent against factor Xa inhibitors; Cirapantag, with promising activity against dabigatran, apixaban, rivaroxaban, edoxaban as well as subcutaneous fondaparinux and low-molecular-weight-heparins. This review article summarizes pharmacological characteristics of these novel antidotes, available clinical and preclinical data, potential indications for clinical use and the need for phase III and IV studies.