CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(06): 998-1005
DOI: 10.1055/s-0041-1740180
New Technologies, Diagnostic Tools and Drugs

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

1   Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
,
Lizhen Xu
1   Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
,
John W. Eikelboom
1   Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
,
Saskia Middeldorp
2   Department of Internal Medicine & Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, The Netherlands
,
Truman J. Milling Jr.
3   Departments of Neurology and Surgery and Perioperative Care, Seton Dell Medical School Stroke Institute, Dell Medical School, University of Texas at Austin, Austin, Texas, United States
,
Mark Crowther
4   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Patrick Yue
5   Portola Pharmaceuticals Inc., now Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
,
Pamela Conley
5   Portola Pharmaceuticals Inc., now Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
,
Genmin Lu
5   Portola Pharmaceuticals Inc., now Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
,
Stuart J. Connolly
1   Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
,
on behalf of the ANNEXA-4 Investigators › Author Affiliations
Funding ANNEXA-4 was funded by Portola Pharmaceuticals Inc., South San Francisco, California, United States, now Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States, following acquisition by Alexion.

Abstract

Background Andexanet alfa (andexanet) is approved for specific anticoagulation reversal in patients with life-threatening or uncontrolled bleeding during treatment with rivaroxaban or apixaban. There is limited experience with andexanet in patients with acute bleeding on edoxaban.

Methods Patients with acute major bleeding within 18 hours of edoxaban intake were prospectively enrolled. Patients received a bolus and 2-hour follow-on infusion of andexanet. The co-primary efficacy outcomes were change in antifactor Xa activity and the percentage of patients achieving excellent or good hemostasis, 12 hours after andexanet treatment. Efficacy was analyzed in patients with confirmed major bleeding and baseline antifactor Xa activity ≥40 ng/mL. Safety was analyzed in all patients.

Results Thirty-six patients (mean age: 82 years, 61.1% male and 91.7% with atrial fibrillation) with acute major bleeding on edoxaban received andexanet. The primary site of bleeding was intracranial in 29 patients (80.6%). In the efficacy population (n = 28), median antifactor Xa activity decreased from 121.1 (interquartile range [IQR]: 70.3–202.4) ng/mL at baseline to 24.0 (IQR: 77.7–83.7) ng/mL at the end of andexanet bolus (median decrease: 68.9%, 95% confidence interval [CI]: 56.1–77.7%). Excellent or good hemostasis at 12 hours was achieved in 78.6% (95% CI: 59.0–91.7%) of patients. Within 30 days, four patients (11.1%) experienced a thrombotic event and four others (11.1%) died.

Conclusion In patients with acute major bleeding on edoxaban, andexanet significantly decreased antifactor Xa activity. Hemostatic efficacy was similar to that observed in patients with bleeding on rivaroxaban or apixaban. Thrombotic events occurred at a rate expected in such patients.

Supplementary Material



Publication History

Received: 28 April 2021

Accepted: 10 October 2021

Article published online:
07 January 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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