Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design.

Autor: Jain SS; Division of Cardiovascular Medicine and the Cardiovascular Institute, Stanford University, Stanford, CA; Stanford Center for Clinical Research, Stanford, CA., Mahaffey KW; Division of Cardiovascular Medicine and the Cardiovascular Institute, Stanford University, Stanford, CA; Stanford Center for Clinical Research, Stanford, CA., Pieper KS; Thrombosis Research Institute, London, United Kingdom., Shimizu W; Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan., Potpara T; School of Medicine, University of Belgrade, Belgrade, Serbia; Cardiology Clinic, University Clinical Center of Serbia, Belgrade, Serbia., Ruff CT; Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Kamel H; Clinical and Translational Neuroscience Unit, Department of Neurology and Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, Cornell University, New York, NY., Lewis BS; Lady Davis Carmel Medical Center and Technion-Israel Institute of Technology, Haifa, Israel., Cornel JH; Noordwest Ziekenhuisgroep, Alkmaar and Radboud, Radboud University Medical Center, Nijmegen, The Netherlands., Kowey PR; Lankenau Institute for Medical Research, Thomas Jefferson University, Philadelphia, PA., Horrow J; Bristol Myers Squibb, Princeton, NJ., Strony J; Janssen Research & Development, LLC, a Johnson & Johnson Company, Raritan, NJ., Plotnikov AN; Janssen Research & Development, LLC, a Johnson & Johnson Company, Raritan, NJ., Li D; Bristol Myers Squibb, Princeton, NJ., Weng S; Janssen Research & Development, LLC, a Johnson & Johnson Company, Raritan, NJ., Donahue J; Stanford Center for Clinical Research, Stanford, CA., Gibson CM; Beth Israel Lahey Health Harvard Medical School and Baim Institute for Clinical Research, Harvard Medical School, Boston, MA., Steg PG; Université Paris-Cité, Assistance Publique-Hôpitaux de Paris, Paris, France., Mehran R; Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Weitz JI; McMaster University, Hamilton, Ontario, Canada., Johnston SC; Department of Neurology, University of California, San Francisco, CA., Hankey GJ; Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Perth, Western Australia, Australia; Perron Institute for Neurological and Translational Science, Perth, Western Australia, Australia., Harrington RA; Weill Cornell Medicine, Cornell University, New York, NY., Lam CSP; National Heart Centre, Singapore, Duke-National University of Singapore (C.S.P.L), Singapore. Electronic address: Carolyn.lam@duke-nus.edu.sg.
Jazyk: angličtina
Zdroj: American heart journal [Am Heart J] 2024 Nov; Vol. 277, pp. 145-158. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1016/j.ahj.2024.08.011
Abstrakt: Background: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk.
Methods: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years.
Conclusion: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter.
Trial Registration: ClinicalTrials.gov NCT05757869.
Competing Interests: Disclosures SSJ reports consulting fees from Bristol Myers Squibb, ARTIS Ventures, and Broadview Ventures outside of the submitted work. KWM’s financial disclosures can be reviewed at http://med.stanford.edu/profiles/kenneth-mahaffey. KSP is a member of The Thrombosis Research Institute which has received institutional research grant support from Anthos Therapeutics and Bayer Pharmaceuticals. She has received honoraria from Element Science and Artivion, Inc. WS has received honoraria (>10K USD) from Daiichi Sankyo, Nippon Boehringer Ingelheim, and Pfizer Japan, and research grants (>50K USD) from Daiichi Sankyo and Nippon Boehringer Ingelheim. CTR reports Research Grants through Institution from: Athos, AstraZeneca, Daiichi Sankyo, Janssen and Novartis. Honoraria for scientific ad boards and consulting from: Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen and Pfizer. He is a member of The TIMI Study Group which has received institutional research grant support through Brigham and Women's Hospital from: Abbott, Abiomed, Inc, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis Pharmaceuticals, Inc, Janssen Research & Development, LLC, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Roche, Saghmos Therapeutics, Inc, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, Verve Therapeutics, Inc, Zora Biosciences. PRK reports consultancy from Anthos, J&J, BMS and Bayer. GS has received research grants from Amarin, AstraZeneca, and Sanofi; has participated in clinical trials, consulting, or speaking for Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Idorsia, Janssen, Novartis, Novo Nordisk, PhaseBio, Pfizer, and Sanofi; is a Senior Associate Editor at Circulation; and serves as the CMO for Bioquantis. RM reports institutional research payments from: Abbott, Affluent Medical, Alleviant Medical, Amgen, AstraZeneca, BAIM, Beth Israel Deaconess Medical Center, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CERC, Chiesi, Concept Medical, Daiichi Sankyo, Duke, Faraday, Idorsia, Janssen, MedAlliance, Medscape, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Pi-Cardia, Protembis, RM Global Bioaccess Fund Management, Sanofi; consultant to Affluent Medical, Boehringer Ingelheim, Chiesi USA, Cordis, Esperion Science/Innovative Biopharma, Gaffney Events, Educational Trust, Global Clinical Trial Partners, Ltd., IQVIA, Medscape/WebMD Global, NovoNordisk, PeerView Institute for Medical Education, TERUMO Europe N.V., Radcliffe and honoararia from AMA and ACC. SCJ has received research support from Jansen, BMS, and AstraZeneca. GJH reports personal honoraria outside the submitted work from the American Heart Association (Associate Editor, Circulation), Bristol Myers Squibb (Steering Committee, AXIOMATIC-SSP trial of milvexian [factor XIa inhibitor] for secondary stroke prevention) and Janssen (Co-chair, Executive Committee, Librexia Stroke trial of milvexian for secondary stroke prevention). RAH has received research grants/contracts from NHLBI (ISCHEMIA), Duke/PCORI (ADAPTABLE), Janssen (Factor Xia inhibitor), CSL (HDL), Baim Institute, UColorado, Harvard (BWH), and Merck; has served as a consultant/advisor for NHLBI (COVID/CONNECTS), Atropos Health, Bitterroot Bio, Bristol Myers Squibb, Bridge Bio, Chiesi, CSL Behring, Edwards Lifesciences Corp, Element Science, Foresight, Merck, and WebMD; and serves on the Board of Directors for AHA and Cytokinetics. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has Received research support from Novo Nordisk and Roche Diagnostics; has Served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Hanmi, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd., Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as Co-founder and nonexecutive director of Us2.ai. The remaining authors report no relevant disclosures or competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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