Andexanet alfa reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion without toxicity, a new study published in The New England Journal of Medicine has shown.1

Factor Xa inhibitors, such as apixaban, rivaroxaban, and edoxaban, are used in the prevention and treatment of thromboembolism; however, no reversal agent currently exists if these agents cause major bleeding or the patient receiving them requires an immediate operation. Therefore, researchers sought to evaluate andexanet, a specific reversal agent that is designed to neutralize the anticoagulant effect of factor Xa inhibitors.

For the study, researchers enrolled 144 healthy older volunteers. Of those, 64 were given apixaban 5 mg twice daily and 70 were given rivaroxaban 20 mg daily. Patients were then randomly given andexamet administered as a bolus or as a bolus plus a 2-hour infusion or placebo.

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Results showed that among apixaban-treated participants, anti-factor Xa activity was reduced by 94% among those who received an andexanet bolus vs 21% among those given placebo (P<.001). Researchers found that thrombin generation was fully restored in 100% and 11%, respectively, within 2 to 5 minutes (P<.001).

Among rivaroxaban-treated participants, anti-factor Xa activity was reduced by 92% in the andexanet bolus group compared with 18% in the placebo group (P<.001). Thrombin generation was fully restored in 96% vs 7% of participants, respectively, (P<.001).

Similar effects were observed in patients who received a bolus plus a 2-hour infusion.

In terms of safety, no serious adverse or thrombotic events occurred.


1. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373:2413-2424.