LIBREXIA ACS Trial: Milvexian Fails to Reduce Cardiovascular Events After ACS
- Investigators previously tested incorporating existing anticoagulants into standard care to reduce recurrent thrombotic events, but this approach led to heightened bleeding hazards.
- Even though therapeutic efficacy was not demonstrated, finding no rise in intracranial or fatal hemorrhages provides comfort given that two additional studies remain underway.
The selective factor XIa inhibitor milvexian failed to reduce major adverse cardiovascular events when added to standard antiplatelet therapy after an acute coronary syndrome, according to findings presented on August 29, 2026, at the ESC Congress 2026 and published simultaneously in the New England Journal of Medicine.
According to the ESC Congress 2026 press release, the LIBREXIA ACS trial evaluated whether oral milvexian could improve cardiovascular outcomes in high-risk patients. The study followed an earlier decision to discontinue the trial in November 2025 due to futility at a preplanned interim analysis. Acute coronary syndrome describes a condition where the heart’s blood supply is suddenly reduced, leaving patients at high risk of recurrent events during the first year even when treated with standard dual antiplatelet therapies, statins, and stents.
Trial Design and Patient Population
Eligible participants in the international trial had experienced an acute coronary syndrome within seven days and had undergone cardiac catheterisation with percutaneous coronary intervention or conservative management, alongside at least two factors associated with increased risk of recurrent ischaemic events. According to the ESC Congress 2026 reporting, a total of 14,194 participants across 893 sites in 44 countries were randomized to receive either oral milvexian 25 mg twice daily or a matched placebo, alongside investigator-determined standard antiplatelet therapy.
Investigators previously tested incorporating existing anticoagulants into standard care to reduce recurrent thrombotic events, but this approach led to heightened bleeding hazards.
Professor P. Gabriel Steg
Professor P. Gabriel Steg from Hôpital Bichat in Paris, France, served as the principal investigator for the trial. He noted that interest has grown around developing factor XIa inhibitors to prevent harmful thrombosis while preserving normal clotting processes to minimize bleeding.
Efficacy and Safety Findings
After a median follow-up of 10 months, the primary efficacy endpoint—which combined cardiovascular death, myocardial infarction, or ischaemic stroke—occurred in 5.4% of patients receiving milvexian and 5.1% of patients receiving placebo, yielding a hazard ratio of 1.05 that was not statistically significant. Researchers observed no difference with milvexian for individual components of the primary endpoint or major secondary efficacy endpoints, including all-cause mortality.
On the safety side, the trial tracked the principal safety endpoint of Bleeding Academic Research Consortium 3c or 5 bleeding, which covers intracranial or fatal bleeding. According to the ESC Congress 2026 data, this safety endpoint occurred in 0.3% of patients in both the milvexian and placebo groups. Laboratory tests confirmed that patients taking milvexian experienced a prolonged activated partial thromboplastin time, demonstrating that the chosen dose produced the expected anticoagulant activity.
Even though therapeutic efficacy was not demonstrated, finding no rise in intracranial or fatal hemorrhages provides comfort given that two additional studies remain underway.
Professor P. Gabriel Steg
Although the LIBREXIA ACS trial did not meet its primary efficacy goals, the safety profile regarding critical bleeding provides important context as researchers continue to evaluate factor XIa inhibition across other thrombotic conditions.