Milvexian does not reduce ischemic events after recent ACS
ESC Congress 2026 – In the phase 3 LIBREXIA ACS trial, adding the factor XIa inhibitor milvexian to standard antiplatelet therapy did not reduce the risk of CV death, MI, or ischemic stroke in patients with a recent ACS compared with placebo, with no significant difference in intracranial or fatal bleeding between groups.
This summary is based on the presentation of Gabriel Steg, MD (Paris, France) at the ESC Congress 2026 - LIBREXIA ACS: Milvexian after recent ACS.
Introduction and methods
Patients remain at increased risk of recurrent ischemic events after ACS despite antiplatelet therapy. Adding low-dose factor Xa inhibition can reduce this risk, but increases the risk of major bleeding. Milvexian is an oral factor XIa inhibitor that demonstrated antithrombotic activity with a low observed risk of major bleeding in a phase 2 study.
LIBREXIA-ACS was designed to determine whether adding milvexian to standard antiplatelet therapy after high-risk ACS could reduce major ischemic CV events without an excessive increase in bleeding.
LIBREXIA ACS was a phase 3, randomized, double-blind, placebo-controlled trial that included adults with a recent ACS (within the previous 7 days) and at least 2 additional risk factors for recurrent ischemic events. Key exclusions included type 2 or periprocedural MI, minimal or no obstructive coronary artery disease, planned staged PCI, an indication for chronic anticoagulation, increased bleeding risk, prior ischemic stroke or TIA, and Killip class 3 or 4. A total of 14,194 patients at 893 sites in 44 countries were randomized 1:1 to oral milvexian 25 mg twice daily (n=7094) or placebo (n=7100), in addition to standard antiplatelet therapy. Randomization was stratified according to the plannend antiplatelet strategy.
The primary efficacy outcome was MACE a composite of CV death, MI, or ischemic stroke. The principal safety outcome was Bleeding Academic Research Consortium (BARC) type 3c or 5 bleeding, comprising intracranial or intraocular bleeding compromising vision or fatal bleeding.
The trial was terminated early for futility in November 2025 after a prespecified interim analysis showed insufficient conditional power to meet the primary efficacy objective.
Main results
Efficacy
- After a median follow-up of 10 months, the primary efficacy outcome of CV death, MI, or ischemic stroke occurred in 5.4% of patients receiving milvexian and 5.1% of those receiving placebo (HR: 1.05; 95%CI: 0.91–1.21; P=0.50).
- There were no differences between milvexian and placebo in the individual components of the primary outcome or in all-cause mortality.
Safety
- BARC type 3c or 5 bleeding occurred in 0.3% of patients in both the milvexian and placebo groups (HR: 1.04; 95%CI: 0.58–1.87; P=0.88).
- There were no significant differences between milvexian and placebo in key secondary bleeding outcomes, including BARC type 3b, 3c or 5 bleeding, non-CABG TIMI major bleeding, and ISTH major bleeding.
Conclusion
In LIBREXIA ACS, adding milvexian to standard antiplatelet therapy after a recent ACS did not reduce the risk of CV death, MI, or ischemic stroke compared with placebo. Milvexian did not increase the risk of BARC type 3c or 5 bleeding. The trial was terminated early for futility following a prespecified interim analysis.
- Our reporting is based on the information provided at the ESC Congress 2026 -