NOACs have an approximate yearly risk of 1% to 3% for major bleeding and a 1% to 2% risk of experiencing a thromboembolic event. There is a dose-response relationship between the NOAC concentrations in the circulation and adverse events. However, the minimum drug level contributing to bleeding or surgical bleeding risk is unknown.
The American College of Cardiology has published its 2020 Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. The introduction of new reversal strategies for NOAC factor Xa inhibitors and more new NOACs to prevent venous thromboembolism prompted this update to 2017 guidelines.
Reversal agents carry a risk of life-threatening thrombosis. They should only be used under the direction of a physician with experience in their use and/or in a patient at imminent risk of death from bleeding. Reversal agents should not be used for most patients with a nonmajor bleeding event.
The FDA has approved two drugs for NOAC anticoagulation reversal therapy.
Idarucizumab
In 2015, Idarucizumab, a humanized monoclonal anti-dabigatran antibody fragment, was approved to reverse the anticoagulant effects of dabigatran, a direct thrombin inhibitor. Currently, this is the only anticoagulant reversal agent for dabigatran for patients with life-threatening bleeding or needing emergency surgery.
Andexanet Alfa
In 2018, Andexanet Alfa, a factor Xa inhibitor medication, was approved as the first and only specific antidote for anticoagulation reversal in patients treated with apixaban and rivaroxaban. Andexanet Alfa is a modified recombinant inactive form of human factor Xa that binds to and blocks the effects of factor Xa inhibitors. Use of the drug should be limited to reverse anticoagulation if needed due to life-threatening or uncontrolled bleeding.
The use of Andexanet Alfa to reverse the effects of edoxaban is currently off-label because more extensive studies are needed to determine its efficacy and safety for this treatment.
