Factor Xa Anticoagulant Reversal with Andexanet

David Green, MD, PhD reviewing Siegal DM et al. N Engl J Med 2015 Nov 11. Connors JM. N Engl J Med 2015 Nov 11.

Participants experienced a >90% decline in the anti-Xa activity of either apixaban or rivaroxaban within 2 to 5 minutes after receiving a 400 mg intravenous bolus of andexanet.

The new oral anti-Xa inhibitors apixaban, edoxaban, and rivaroxaban have advantages over vitamin K antagonists, but the absence of an anti-Xa reversal agent has limited their widespread adoption. Andexanet is a compound that binds tightly to the active site of these anti-Xa anticoagulants, preventing further inhibition of factor Xa.

To examine the safety and efficacy of andexanet, investigators conducted an industry-sponsored, double-blind, placebo-controlled, phase II trial in nonbleeding adults aged 50 to 75. Participants received either apixaban (5 mg) or rivaroxaban (20 mg) for 4 days followed by a 400 mg intravenous bolus of andexanet; some subjects then received a 2-hour continuous intravenous infusion of andexanet. The primary endpoint was the percent change in anti-Xa activity.

Within 2 to 5 minutes of receiving the andexanet bolus, participants experienced a >90% decline in the anti-Xa activity of either apixaban or rivaroxaban. The reduction of anti-Xa activity persisted for up to 2 hours after the andexanet bolus, whether given with or without an infusion. All andexanet recipients but one, who did not receive the full dose of andexanet, had a ≥80% reversal of anti-Xa activity (P<0.001). No serious adverse events were associated with andexanet, but one recipient developed urticaria during the infusion, which resolved with discontinuation of the drug and administration of an antihistamine.

Citation(s):

Siegal DM et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 2015 Nov 11; [e-pub].

Connors JM.Antidote for factor Xa anticoagulants. N Engl J Med 2015 Nov 11; [e-pub].