Physicians' Academy for Cardiovascular Education

Anticoagulation reversal in patients with acute bleeding during oral factor Xa inhibitor therapy

Andexanet Alfa for Specific Anticoagulation Reversal in Patients with Acute Bleeding during Treatment with Edoxaban

Literature - Benz AP, Xu L, Eikelboom JW et al. - Thromb Haemost. 2022 Jan 7. doi: 10.1055/s-0041-1740180.

Introduction and methods

Background

Patients on anticoagulant therapy who experience acute bleeding, such as an intracranial hemorrhage, need rapid and specific anticoagulation reversal to restore hemostasis [1-3]. Andexanet alfa (andexanet) specifically binds and sequesters factor Xa inhibitors [4-5]. It is approved for specific anticoagulation reversal in patients on rivaroxaban and apixaban with life-threatening or uncontrolled bleeding. There is limited data on the efficacy and safety of andexanet in patients with acute major bleeding on edoxaban.

Aim of the study

This prospective, single-arm cohort study assessed the efficacy and safety of andexanet in 36 patients with acute major bleeding on edoxaban.

Methods

36 patients (mean age was 81.5 years, 61.1% were male and 91.7% with AF as primary indication for oral anticoagulation) with acute major bleeding within 18 hours of edoxaban intake were included in this study.

Patients received a bolus of andexanet and a subsequent follow-on infusion over 2 hours. The dosing regiment depended on the dosage and time of the last edoxaban dose. Patients who had received an >30 mg or unknown dose of edoxaban within <8 hours or unknown time received an andexanet bolus of 800 mg and follow-on infusion of 960 mg. Patients who had received ≤30 mg of edoxaban within <8 hours or unknown time and patients who had received their last dose of edoxaban ≥8 hours before received an andexanet bolus of 400 mg and a follow-on infusion of 480 mg.

Efficacy was analyzed in two different populations: 1) Patients with confirmed major bleeding and baseline antifactor Xa activity ≥40 ng/mL (n=28) and 2) Patients with confirmed major bleeding and baseline antifactor Xa activity ≥75 ng/mL (n=20). Safety was analyzed in all patients (n=36).

Outcomes

The co-primary efficacy outcomes were median percent change in antifactor Xa activity from baseline to end of andexanet bolus and the percentage of patients achieving excellent or good hemostasis at 12 hours after treatment with andexanet according to criteria adapted from [6]. Hemostatic efficacy was reviewed by an independent endpoint adjudication committee.

Safety outcomes were thrombotic events (MI, stroke, TIA, DVT, PE, and SE) and death up until 30 days after andexanet treatment.

Main results

Efficacy outcome: Median percent change in antifactor Xa activity

Efficacy outcome: Percentage of patients achieving excellent or good hemostasis

Safety outcome

Conclusion

Andexanet decreased median antifactor Xa activity in patients on edoxaban with an acute major bleeding. Excellent hemostasis at 12 hours after andexanet administration was achieved in 78.6% of patients with baseline antifactor Xa activity ≥40 ng/mL and in 75.0% with baseline antifactor Xa activity ≥75 ng/mL.

Thrombotic events and deaths at 30 days after andexanet treatment occurred at a similar rate compared to patients on other oral factor Xa inhibitors who received andexanet for acute bleeding [5].

References

Show references

Find this article online at Thromb Haemost.

Share this page with your colleagues and friends: