Key takeaways
Munich, Germany – 29 August 2026: Milvexian did not reduce major adverse cardiovascular events compared with placebo after a recent acute coronary syndrome and there was no increase in intracranial or fatal bleeding. These were the main findings from the LIBREXIA ACS trial presented in a Hot Line session today at ESC Congress 20261 and published simultaneously in the New England Journal of Medicine. The results follow a decision to discontinue the trial in November 2025 due to futility at a preplanned interim analysis.
Acute coronary syndrome (ACS), one of the most complex and challenging settings in cardiovascular care, describes a condition in which the heart’s blood supply is suddenly reduced, such as during a myocardial infarction (MI). The risk of another cardiovascular event remains high during the year after ACS, even with the use of standard therapies including dual antiplatelet therapies, statins and stents.
“Adding current anticoagulants to standard therapy has been tested to reduce recurrent thrombotic events, but bleeding risk was increased,” explained Principal Investigator of the LIBREXIA ACS trial, Professor P. Gabriel Steg from Hôpital Bichat, Paris, France, who continued: “There has been increasing interest in developing factor XIa inhibitors to prevent harmful thrombosis, while preserving normal clotting processes to minimise bleeding. We conducted the LIBREXIA ACS trial to assess the efficacy and safety of the selective factor XIa inhibitor, milvexian, after ACS when added to standard antiplatelet therapy.”
Eligible participants had had an ACS within seven days and had undergone cardiac catheterisation with percutaneous coronary intervention or were being managed conservatively. Additionally, participants had to have at least two factors associated with increased risk of recurrent ischaemic events. All patients received standard antiplatelet therapy as determined by the investigator. A total of 14,194 participants at 893 sites in 44 countries were randomised to oral milvexian 25 mg twice daily or a matched placebo.
The Independent Data Monitoring Committee recommended discontinuing the trial after a preplanned interim analysis showed that it was unlikely to meet its primary endpoint. Futility was confirmed when the data were subsequently analysed. After a median follow-up of 10 months, the primary efficacy endpoint of cardiovascular death, MI or ischaemic stroke occurred at a similar incidence in both groups: 5.4% of patients with milvexian and 5.1% of patients with placebo (hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.91 to 1.21; p=0.50).
No difference was observed with milvexian for the individual components of the primary endpoint or any major secondary efficacy endpoints, including all-cause mortality.
The researchers found no difference in the principal safety endpoint of Bleeding Academic Research Consortium (BARC) 3c or 5 bleeding (intracranial or fatal bleeding), which occurred in 0.3% of patients with milvexian and placebo (HR 1.04; 95% CI 0.58 to 1.87; p=0.88).
Patients in the milvexian group had a prolonged activated partial thromboplastin time suggesting that the dose of milvexian had the expected anticoagulant activity.
Discussing the implications of these findings, Professor Steg said: “While no effect on efficacy was shown, the absence of an observed increase in intracranial or fatal bleeding is reassuring given that two further trials are ongoing: LIBREXIA AF for patients with atrial fibrillation and LIBREXIA Stroke for secondary stroke prevention. These studies are distinct from LIBREXIA ACS in several aspects, including patient populations, endpoints, type and duration of background therapy and disease pathology.”
ENDS