Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design - 05/09/24

Doi : 10.1016/j.ahj.2024.08.011

Sneha S. Jain, MD, MBA ^a,^b, Kenneth W. Mahaffey, MD ^a,^b, Karen S. Pieper, MS ^c, Wataru Shimizu, MD, PhD ^d, Tatjana Potpara, MD, PhD ^e, Christian T. Ruff, MD, MPH ^f, Hooman Kamel, MD, MS ^g, Basil S. Lewis, MD ^h, Jan H. Cornel, MD ⁱ, Peter R. Kowey, MD ^j, Jay Horrow, MD ^k, John Strony, MD ^l, Alexei N. Plotnikov, MD ^l, Danshi Li, MD, PhD ^k, Stephen Weng, PhD ^l, Julia Donahue, BA ^b, C. Michael Gibson, MS, MD ^m, P. Gabriel Steg, MD ⁿ, Roxana Mehran, MD ^o, Jeffrey I. Weitz, MD ^p, S. Claiborne Johnston, MD, PhD ^q, Graeme J. Hankey, MBBS, MD ^r,^s, Robert A. Harrington, MD ^t, Carolyn S.P. Lam, MBBS, PhD ^u,^⁎
on behalf of the
LIBREXIA AF Trial Investigators and Committees
^a Division of Cardiovascular Medicine and the Cardiovascular Institute, Stanford University, Stanford, CA
^b Stanford Center for Clinical Research, Stanford, CA
^c Thrombosis Research Institute, London, United Kingdom
^d Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
^e School of Medicine, University of Belgrade, Belgrade, Serbia; Cardiology Clinic, University Clinical Center of Serbia, Belgrade, Serbia
^f Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
^g Clinical and Translational Neuroscience Unit, Department of Neurology and Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, Cornell University, New York, NY
^h Lady Davis Carmel Medical Center and Technion‐Israel Institute of Technology, Haifa, Israel
ⁱ Noordwest Ziekenhuisgroep, Alkmaar and Radboud, Radboud University Medical Center, Nijmegen, The Netherlands
^j Lankenau Institute for Medical Research, Thomas Jefferson University, Philadelphia, PA
^k Bristol Myers Squibb, Princeton, NJ
^l Janssen Research & Development, LLC, a Johnson & Johnson Company, Raritan, NJ
^m Beth Israel Lahey Health Harvard Medical School and Baim Institute for Clinical Research, Harvard Medical School, Boston, MA
ⁿ Université Paris-Cité, Assistance Publique-Hôpitaux de Paris, Paris, France
^o Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY
^p McMaster University, Hamilton, Ontario, Canada
^q Department of Neurology, University of California, San Francisco, CA
^r Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Perth, Western Australia, Australia
^s Perron Institute for Neurological and Translational Science, Perth, Western Australia, Australia
^t Weill Cornell Medicine, Cornell University, New York, NY
^u National Heart Centre, Singapore, Duke-National University of Singapore (C.S.P.L), Singapore

^⁎Reprint requests: Carolyn S.P. Lam, MBBS, PhD, National Heart Centre Singapore, Duke-National University of Singapore (C.S.P.L), 5 Hospital Drive, 169609 SingaporeNational Heart Centre SingaporeDuke-National University of Singapore (C.S.P.L)5 Hospital Drive169609Singapore

Résumé

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

Le texte complet de cet article est disponible en PDF.

Graphical Abstract

LIBREXIA AF Study Design. LIBREXIA AF is a randomized, double-blind, double-dummy, parallel-group, multicenter, event-driven, active-controlled study. Approximately 15,500 participants with permanent or paroxysmal AF are being enrolled and followed until the prespecified number of endpoint events is observed. At the end of treatment visit, clinicians are encouraged to place participants on open-open label apixaban, which will be provided by the sponsor for 30 days.

Image, graphical abstract

Le texte complet de cet article est disponible en PDF.

Plan

Intervention and follow-up

Dosing considerations

Concurrent interventions

Efficacy and safety evaluations

Statistical methods and considerations

Administrative organization

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Vol 277

P. 145-158 - novembre 2024 Retour au numéro

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Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design - 05/09/24

Résumé

Background

Methods

Conclusion

Trial registration

Graphical Abstract

Plan

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