Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors

作者：Joshua N. Goldstein, Truman J. Milling, John W. Eikelboom, C. Michael Gibson, John T. Curnutte, Alex Gold, Michele Bronson, Genmin Lu, Pamela B. Conley, Peter Verhamme, Jeannot Schmidt, Saskia Middeldorp, Alexander T. Cohen, Jan Beyer‐Westendorf, Pierre Albaladejo, José López‐Sendón, Shelly Goodman, Janet M. Leeds, Brian L. Wiens, Deborah Siegal, Elena Zotova, Brandi Meeks, Juliet Nakamya, W. Ting Lim, Mark Crowther · 发表于：New England Journal of Medicine · 年份：2016 · DOI：10.1056/nejmoa1607887 · 被引用次数：790 · 研究领域：Atrial Fibrillation Management and Outcomes、Blood Coagulation and Thrombosis Mechanisms、Trauma, Hemostasis, Coagulopathy, Resuscitation

BACKGROUND: Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. METHODS: In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. RESULTS: The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. ...