Antidotes for the direct oral anticoagulants: What news?

The direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulants for both stroke prevention in patients with non-valvular atrial fibrillation and the treatment and secondary prevention of venous thromboembolism. DOACs cause bleeding, albeit less than warfarin. Most bleeding complications can be controlled by general reversal strategies and supportive care. However, in case of life-threatening bleeding, or when urgent invasive procedures are needed, a more rapid and thorough reversal may be required. Idarucizumab, andexanet alfa and ciraparantag have been developed as reversal agents for the DOACs. To date idarucizumab is the only approved antidote and is specific for dabigatran. Andexanet alfa, a reversal agent for the factor Xa inhibitors, is still under investigation, but its approval by regulatory agencies is expected soon. Ciraparantag, a universal antidote, is in an earlier stage of development. Based on the results of clinical trials to date, these compounds appear to be breakthrough for urgent and emergency reversal. When administered at fixed doses, they ensured a rapid, efficient and safe restoration of haemostasis. From a practical perspective, all hospitals should develop local protocols to ensure safe and efficient clinical implementation of reversal strategies. Post-marketing studies will be essential to assess the evolution of management strategies and to confirm the safety and effectiveness of these agents.