Andexanet alfa may be efficacious in decreasing anticoagulant activity of factor Xa inhibitors, according to research published in the New England Journal of Medicine.

In this prospective, open label, nonrandomized study (ANNEXA-4; Identifier: NCT02329327), 352 patients (mean age, 77 years) who exhibited acute major bleeding within 18 hours of receiving a factor Xa inhibitor were enrolled. Andexanet was administered first as a bolus and then as a 2-hour infusion. Primary efficacy outcomes included percentage of patients with good or excellent hemostatic efficacy at 12 hours and percent change in antifactor Xa activity. Primary safety outcomes included death and incidence of thrombotic events.

Patients exhibited primarily intracranial (64%) or gastrointestinal (26%) bleeding. Median antifactor Xa activity decreased from baseline by 92% in patients who received apixaban (149.7 ng/mL to 11.1 ng/mL), 92% in patients who received rivaroxaban (211.8 ng/mL to 14.2 ng/mL), and 75% in patients who received enoxaparin (0.48 IU/mL to 0.15 IU/mL).

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Of 249 evaluable patients, 204 (82%) exhibited good or excellent hemostatic efficacy. There were 49 (14%) patient deaths within 30 days of treatment, and thrombotic events occurred in 34 (10%) patients. Reduction in antifactor Xa activity was slightly predictive of hemostatic efficacy in patients with intracranial bleeding but was not predictive overall.

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Anticoagulant therapy was reinitiated in 220 (62%) patients within 30 days of andexanet therapy. Thrombotic events occurred during follow-up in 8 patients who were restarted on parenteral anticoagulation; no patients who were restarted on oral anticoagulation experienced a thrombotic event during follow-up.

The authors concluded that andexanet alfa yielded significant decreases in antifactor Xa activity in patients with acute major bleeding resulting from use of a factor Xa inhibitor. Another trial ( Identifier: NCT03661528) utilizing a prospective, randomized, controlled design to study the safety and efficacy of andexanet alfa in patients with acute intracranial bleeding is currently under way.


1. Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors [published online February 7, 2019]. New Engl J Med. doi: 10.1056/NEJMoa1814051