Andexanet quickly reverses factor Xa inhibitor activity for DOACs
Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet alpha is designed to reverse the anticoagulant effects of factor Xa inhibitors.
In a recent study, healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebo-controlled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti–factor Xa activity.
In apixaban-treated participants, anti–factor Xa activity was reduced by 94% among those who received an andexanet bolus, vs. 21% among those who received placebo. Thrombin generation was fully restored in 100% vs. 11% of the participants within 2 to 5 minutes. Among the rivaroxaban-treated participants, anti–factor Xa activity was reduced by 92% among those who received an andexanet bolus vs. 18% among those who received placebo. Thrombin generation was fully restored in 96% vs. 7% of the participants. These effects were sustained when andexanet was administered as a bolus plus an infusion. No serious adverse or thrombotic events were reported.
The manufacturer is pursuing an accelerated approval pathway with the FDA.
Siegal DM, Curnutte JT, Connolly SJ et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. NEJM 2015. Published online before print Nov 11,2015:DOI: 10.1056/NEJMoa1510991.