The use of andexanet alfa (andexanet) in patients with acute major bleeding following an Xa inhibitor may “rapidly reverse anti-factor Xa activity,” according to preliminary results from the ANNEXA-4 trial presented Aug. 30 during ESC Congress 2016 in Rome and simultaneously published in the New England Journal of Medicine.

The study, led by Stuart J. Connolly, MD, FACC, et al., looked at 67 patients with acute major bleeding within 18 hours after the administration of a factor Xa inhibitor: apixaban, rivaroxaban, edoxaban or enoxaparin. The mean age was 77 years and all patients had a history of thrombotic events and cardiovascular disease. Primary sites of bleeding were gastrointestinal (49 percent) and intracranial (42 percent). Patients received an initial bolus of andexanet followed by a two-hour infusion of the drug. Dosing was based on which factor Xa (fXa) inhibitor they had been exposed to, and when. Patients were assessed at baseline, end-of-bolus, and end of the two-hour infusion, as well as at four, eight and 12 hours, and three and 30 days post-infusion.

Overall results showed andexanet reduced anticoagulant activity by roughly 90 percent within 30 minutes among patients with acute major bleeding while receiving a fXa inhibitor. “Excellent or good” hemostasis was achieved within 12 hours after the andexanet infusion in 79 percent of patients. Additionally, thrombotic events occurred in 18 percent of patients during the 30-day follow-up. “This rate of events is not unexpected considering the thrombotic potential of the patients and the fact that in most of them anticoagulation was discontinued at the time of bleeding and not restarted,” noted Connolly.

According to the study authors, further analysis of the data following additional enrollment “should provide details regarding the relationship between the reduction in anti-factor Xa activity and clinical hemostatic outcomes.” They suggest that “a controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events.” 

Keywords: ESC Congress, Factor Xa, Factor Xa Inhibitors, Hemorrhage

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