Reversal Strategies for NOACs: State of Development, Possible Clinical Applications and Future Perspectives

The non-vitamin K antagonist oral anticoagulants (NOACs) are used for thromboembolic prophylaxis of patients with atrial fibrillation and in the treatment as well as secondary prophylaxis of patients with venous thromboembolism. Even though NOACs have a better safety profile than vitamin K antagonists (VKAs), there will still be bleeding complications on NOAC treatment. In some cases, stopping the NOAC and non-drug-related management such as manual compression and interventional endoscopy will be sufficient to stop the bleeding. In more serious bleeding events and before acute surgery, coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants including NOACs is currently undergoing phase II trials. For use of these specific antidotes, it is desirable that measurements for coagulation activity with a short response delay are widely available for the different NOACs and further research in this field is needed. Furthermore, guidelines for antidote use, including general measures for the treatment of NOAC-related bleeding, should be available.