Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event
Abstract
BackgroundPatients are at increased risk for recurrent ischemic events after an acute coronary syndrome event. Milvexian, an oral factor XIa inhibitor, may reduce the risk of major adverse clinical events with minimal bleeding risk. MethodsIn this phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of milvexian when added to standard antiplatelet therapy within 7 days after an acute coronary syndrome event. Patients were assigned in a 1:1 ratio to receive oral milvexian (25 mg twice daily) or matched placebo. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke as evaluated in a time-to-event analysis. The principal safety outcome was Bleeding Academic Research Consortium (BARC) type 3c or 5 bleeding (intracranial or intraocular bleeding that compromises vision or fatal bleeding). ResultsAfter a planned interim analysis that was based on 556 adjudicated efficacy end points, the trial was terminated for futility. A total of 14,194 patients had been enrolled, with 7094 assigned to receive milvexian and 7100 to receive placebo. After a median follow-up of 12.2 months, a primary efficacy outcome event had occurred in 384 patients (5.4%) in the milvexian group and in 365 patients (5.1%) in the placebo group (hazard ratio, 1.05; 95% confidence interval, 0.91 to 1.21; P=0.50). BARC type 3c or 5 bleeding occurred in 23 patients (0.3%) in the milvexian group and in 22 patients (0.3%) in the placebo group (P=0.88). ConclusionsAmong patients with a recent acute coronary syndrome event, milvexian did not decrease the risk of cardiovascular death, myocardial infarction, or ischemic stroke but did not increase the risk of intracranial or fatal bleeding, as compared with placebo. (Funded by Janssen Research and Development and Bristol Myers Squibb; LIBREXIA ACS ClinicalTrials.gov number, NCT05754957.)
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Authors: C. Michael Gibson, Philippe Gabríel Steg, M. Cecilia Bahit, Rasha Al-Lamee, Shamir R. Mehta, Roxana Mehran, Jeffrey I. Weitz, Shinya Goto, José Carlos Nicolau, Renato D. Lopes, Junbo Ge, Nebojša Tasić, Dominick J. Angiolillo, Suzanne J. Baron, Ajay J. Kirtane, Denis Xavier, Satoshi Yasuda, Basil S. Lewis, Duk‐Woo Park, Jan H. Cornel, Tom Johnson, Jarosław Trębacz, Daniel Duerschmied, Christoph Bode, Bela Merkely, Maria Dorobantu, Dragoş Vinereanu, Zuzana Motovska, Héctor Bueno, Jose Luis Lopez-Sendon, Grégory Ducrocq, Giuseppe Ambrosio, Lesley Burgess, Allan BOHM, Chern‐En Chiang, João Morais, Alan Fong, Ümit Güray, José L. Leiva-Pons, Pascal Vranckx, Harvey D. White, Sasko Kedev, Marco Valgimigli, Duško Cerovec, Dimitris Tousoulis, Gemma Figtree, Thuong Dung Ho, Rody G. Sy, Morten Bøttcher, Kurt Huber, Rimvydas Šlapikas, Andrejs Ērglis, Jack Wei Chieh Tan, Christian Pincetti, Karen S. Pieper, Kenneth W. Mahaffey, Carolyn S.P. Lam, S. Claiborne Johnston, Graeme J. Hankey, Luke Zheng, Ronald Aronson, Danshi Li, Ravi Notani, Philippe Vieira Pires, Thomas J. Povsic, Alistair C Lindsay, Alexei Plotnikov, Hsiaowei Deng, Elliot S. Barnathan, Robert A. Harrington
Institutions: University of Florida, The University of Sydney, Johnson & Johnson (United States), Imperial College London, Fudan University, Zhongshan Hospital, Sun Yat-sen University, Jacksonville University, Harvard University, University Hospitals Bristol NHS Foundation Trust, Cornell University, Duke University, Semmelweis University, Ulsan College, Heidelberg University, University Hospital Heidelberg, National University of Singapore, Lithuanian University of Health Sciences, Radboud University Nijmegen, University of Ulsan, Asan Medical Center, National Heart Foundation of Australia, Charles University, Stanford University, Université Paris Cité, Sorbonne Paris Cité, Sağlık Bilimleri Üniversitesi, Tohoku University, Aarhus University, University Medical Center Hamburg-Eppendorf, Carol Davila University of Medicine and Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Universidad Autónoma de Madrid, Research Institute Hospital 12 de Octubre, Taipei Veterans General Hospital, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, McMaster University, Columbia University Irving Medical Center, Perron Institute for Neurological and Translational Science, Massachusetts General Hospital, Bilkent University, Pauls Stradiņš Clinical University Hospital, National and Kapodistrian University of Athens, Stellenbosch University, Hospital de Santo António, University of Perugia, Weill Cornell Medicine, University Medical Centre Mannheim, Radboud University Medical Center, Hospital La Paz Institute for Health Research, Comenius University Bratislava, Hamilton Health Sciences, University Hospital Kralovske Vinohrady, Tokai University, Bristol-Myers Squibb (United States), University Medical Center HCMC, Universitäts-Herzzentrum Freiburg-Bad Krozingen, University Hospitals Bristol and Weston NHS Foundation Trust, National Heart Centre Singapore, Instituto de Neurología Cognitiva, Carmel Medical Center, Thrombosis Research Institute, Universidad Católica de Temuco, Philippine General Hospital, Auckland City Hospital, Baim Institute for Clinical Research, Mount Sinai Medical Center, Regionshospitalet Herning, National University Heart Centre Singapore, Heart Foundation, Associazione Italiana Arbitri, St.John's Medical College Hospital, Institute for Cardiovascular Diseases of Vojvodina, Tygerberg Hospital, John Paul II Hospital, Alliance nationale pour les sciences de la vie et de la santé, Thrombosis and Atherosclerosis Research Institute, NIHR Bristol Cardiovascular Biomedical Research Unit, Epix Pharmaceuticals (United States), Sarawak Biodiversity Centre, Universidad del Centro de México, Hartcentrum Hasselt, PHI University Psychiatric Clinic - Skopje, Istituto Cardiocentro Ticino, University of Applied Sciences Burgenland, DELL (United States)