@article{5f67e5df249f4ece94e41a0d17e7dc3c,
title = "Restart of Anticoagulant Therapy and Risk of Thrombosis, Rebleeding, and Death after Factor Xa Inhibitor Reversal in Major Bleeding Patients",
abstract = "Background Lack of data on balancing bleeding and thrombosis risk causes uncertainty about restarting anticoagulants after major bleeding. Anticoagulant reversal trials offer prospectively gathered data after major bleeding with well-documented safety events and restarting behavior. Objectives To examine the relationship of restarting anticoagulation with thrombosis, rebleeding, and death. Methods This is a posthoc analysis of a prospective factor Xa inhibitor reversal study at 63 centers in North America and Europe. We compared outcomes of restarted patients with those not restarted using landmark and time-dependent Cox proportional hazards models. Outcomes included thrombotic and bleeding events and death and a composite of all three. Results Of 352 patients enrolled, oral anticoagulation was restarted in 100 (28%) during 30-day follow-up. Thirty-four (9.7%) had thrombotic events, 15 (4.3%) had bleeding events (after day 3), and 49 (14%) died. In the landmark analysis comparing patients restarted within 14 days to those not, restarting was associated with decreased thrombotic events (hazard ratio [HR] = 0.112; 95% confidence interval [CI]: 0.001-0.944; p = 0.043) and increased rebleeding (HR = 8.39; 95% CI: 1.13-62.29; p = 0.037). The time-dependent Cox model showed evidence for a reduction in a composite (thrombotic events, bleeding, and death) attempting to capture net benefit (HR = 0.384; 95% CI: 0.161-0.915; p = 0.031). Conclusion This analysis provides modest evidence that restarting anticoagulation in factor Xa inhibitor-associated major bleeding patients is correlated with reduced risk of thrombotic events and increased risk of rebleeding. There is low-level evidence of net benefit for restarting. A randomized trial of restarting would be appropriate.",
keywords = "prevention, pulmonary embolism, stroke, thrombosis, venous thromboembolism",
author = "Milling, {Truman J.} and Ben King and Patrick Yue and Saskia Middeldorp and Jan Beyer-Westendorf and Eikelboom, {John W.} and Mark Crowther and Lizhen Xu and Peter Verhamme and Siegal, {Deborah M.} and Connolly, {Stuart J.}",
note = "Funding Information: T.J.M.: CSL Behring: consulting; Portola: grant support, steering committee; Octapharma: steering committee. B.K.: none. P.Y.: Portola: employee. S.M.: Daiichi Sankyo, Bayer, Aspen Pharma: grant support; Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Portola: advisory board; Portola: lecture fees; AbbVie: adjudication committee. J.B.-W.: Bayer, Daiichi Sankyo: grant support, lecture fees, advisory board fees; Pfizer: grant support; Portola: lecture fees, advisory board fees. J.W.E.: Astra-Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Sanofi-Aventis: grant support, honoraria. M.C.: Bristol Myers Squibb Canada, Asahi Kasei, Servier Canada, Precision Biologics, Hemostasis Reference Laboratory, CSL Behring: advisory board; Alexion, Pfizer, CSL Behring, Diagnostica Stago: educational funding; Bayer, Leo Pharma: grant support; Daiichi Sankyo, Bayer, Octa-pharma: data safety monitoring board. L.X.: None. P.V.: Bayer Healthcare, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, Bristol Myers Squibb, Leo Pharma: grant support, consulting, lecture fees; Boehringer Ingelheim: adjudication committee; Anthos, Janssen, Portola: consulting. D.M.S.: Bayer, Bristol Myers Squibb/Pfizer, Servier Canada, Novartis, Leo Pharma, Aspen Pharma, Portola: consulting. S.J.C.: Portola, Bristol Myers Squibb, Bayer, Daiichi Sankyo: grant support, consulting; Javelin: consulting. Funding Information: This study was funded by Portola Pharmaceuticals, Inc., South San Francisco, California, United States, now Alex-ion Pharmaceuticals, Inc., Boston, Massachusetts, United States, following acquisition by Alexion. Editorial support was provided by Cello Health Communications and funded by Alexion Pharmaceuticals, Inc. Publisher Copyright: {\textcopyright} 2021 Georg Thieme Verlag. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = aug,
day = "1",
doi = "https://doi.org/10.1055/a-1400-6159",
language = "English",
volume = "121",
pages = "1097--1106",
journal = "Thrombosis and haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "8",
}