@article{ee90a618825447078c0931414612476b,
title = "Andexanet Alfa for Specific Anticoagulation Reversal in Patients with Acute Bleeding during Treatment with Edoxaban",
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.",
keywords = "andexanet alfa, bleeding, edoxaban, intracranial hemorrhage, reversal",
author = "Benz, {Alexander P.} and Lizhen Xu and Eikelboom, {John W.} and Saskia Middeldorp and Milling, {Truman J.} and Mark Crowther and Patrick Yue and Pamela Conley and Genmin Lu and Connolly, {Stuart J.}",
note = "Funding Information: The ANNEXA-4 study was jointly designed and planned by the Population Health Research Institute at McMaster University, Hamilton, Ontario, Canada, and the manufacturer of andexanet, Portola Pharmaceuticals, now Alexion, AstraZe-neca Rare Disease, Boston, Massachusetts, United States. The study was funded by Portola Pharmaceuticals. The study was coordinated and all statistical analyses were performed at the Population Health Research Institute. The sponsor was not involved in data collection but did have access to the data. Funding Information: A.P.B and L.X. have nothing to report. J.W.E. reports honoraria and/or research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daii-chi Sankyo Inc., Pfizer, and Servier. S.M. reports grant support from Daiichi Sankyo Inc., Bayer, and Aspen Pharma; serving on advisory boards for Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, and Portola; receiving lecture fees from Portola; and serving on an adjudication committee for AbbVie. T.J.M. reports executive/steering committee payments for ANNEXA-I and ENRICH-AF studies from PHRI/McMaster University; consulting income from CSL Behring; and grants from NHLBI and Genentech. M.C. reports serving on a data and safety monitoring board for Bayer; receiving personal funding or serving on advisory boards for Bristol Myers Squibb Canada, CSL Behring, Servier Canada, Asahi Kasei, Precision Biologics, and Hemostasis Reference Laboratory; preparation of educational material and/or presentations and/or moderation of sessions for Pfizer, Alexion, CSL Behring, and Diagnostica Stago; and individual stock ownership for Alnylam. P.Y. reports former employment with Portola Pharmaceuticals Inc., now Alexion, AstraZe-neca Rare Disease. P.C. reports former employment with Portola Pharmaceuticals Inc., now Alexion, AstraZeneca Rare Disease. G.L. reports employment with Portola Pharmaceuticals Inc., now Alexion, AstraZeneca Rare Disease. S.J.C. reports institutional research grants and honoraria from Boehringer Ingelheim, Portola/Alexion Pharmaceuticals, Bristol-Myers Squibb/Pfizer, Bayer, and Daiichi San-kyo Inc. Publisher Copyright: {\textcopyright} 2022 Georg Thieme Verlag. All rights reserved.",
year = "2022",
month = jun,
day = "1",
doi = "https://doi.org/10.1055/s-0041-1740180",
language = "English",
volume = "122",
pages = "998--1005",
journal = "Thrombosis and haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "6",
}