C Michael Gibson, P Gabriel Steg, M Cecilia Bahit, Rasha Al-Lamee, Shamir R Mehta, Roxana Mehran, Jeffrey I Weitz, Shinya Goto, Jose Carlos Nicolau, Renato D Lopes, Junbo Ge, Nebojsa Tasic, Dominick J Angiolillo, Suzanne J Baron, Ajay J Kirtane, Denis Xavier, Satoshi Yasuda, Basil S Lewis, Duk-Woo Park, Jan H Cornel, Thomas W Johnson, Jaroslaw Trebacz, Daniel Duerschmied, Christoph Bode, Bela Merkely, Maria Dorobantu, Dragos Vinereanu, Zuzana Motovska, Hector Bueno, Jose Luis Lopez-Sendon, Gregory Ducrocq, Giuseppe Ambrosio, Lesley Burgess, Allan Bohm, Chern-En Chiang, Joao Morais, Alan Fong, Umit Guray, Jose Luis 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 Slapikas, Andrejs Erglis, 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, LIBREXIA ACS Committees and Investigators
Among 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.).
BACKGROUND: Patients 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.
METHODS: In 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).
RESULTS: After 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).
CONCLUSIONS: Among 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.).