Milvexian Fails to Reduce Cardiovascular Events After Acute Coronary Syndrome in LIBREXIA ACS Trial
核心洞察
The LIBREXIA ACS trial found milvexian did not reduce major adverse cardiovascular events compared with placebo after recent acute coronary syndrome (搜索) (HR 1.05; 95% CI 0.91–1.21; p=0.50).
The primary efficacy endpoint of cardiovascular death, MI, or ischemic stroke (搜索) occurred in 5.4% of milvexian patients versus 5.1% of placebo patients after a median 10-month follow-up.
No increase in intracranial or fatal bleeding (BARC 3c or 5) was observed, with events in 0.3% of both groups (HR 1.04; p=0.88).
Milvexian, a selective factor XIa (搜索) inhibitor, did not reduce major adverse cardiovascular events compared with placebo in patients with a recent acute coronary syndrome (搜索) (ACS), according to results from the LIBREXIA ACS trial presented in a Hot Line session at ESC Congress 2026 and published simultaneously in the New England Journal of Medicine. The findings follow a decision to discontinue the trial in November 2025 due to futility at a preplanned interim analysis.
The trial enrolled 14,194 participants across 893 sites in 44 countries, making it one of the largest Hot Line studies presented at the congress. Eligible participants had experienced an ACS within seven days and had undergone cardiac catheterisation with percutaneous coronary intervention or were being managed conservatively. Additionally, participants were required to have at least two factors associated with increased risk of recurrent ischemic events. All patients received standard antiplatelet therapy as determined by the investigator, and were randomized to oral milvexian 25 mg twice daily or a matched placebo.
Primary Efficacy Endpoint Not Met
After a median follow-up of 10 months, the primary efficacy endpoint of cardiovascular death, myocardial infarction (搜索) (MI), or ischemic stroke (搜索) occurred at a similar incidence in both groups: 5.4% of patients receiving milvexian and 5.1% of patients receiving 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.
Safety Findings
The researchers found no difference in the principal safety endpoint of Bleeding Academic Research Consortium (BARC) 3c or 5 bleeding, defined as intracranial or fatal bleeding, which occurred in 0.3% of patients in both the milvexian and placebo groups (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.
Rationale and Clinical Context
Acute coronary syndrome (搜索) describes a condition in which the heart's blood supply is suddenly reduced, such as during a myocardial infarction (搜索). 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. This has driven increasing interest in developing factor XIa (搜索) inhibitors to prevent harmful thrombosis while preserving normal clotting processes to minimize bleeding.
"We conducted the LIBREXIA ACS trial to assess the efficacy and safety of the selective factor XIa (搜索) inhibitor, milvexian, after ACS when added to standard antiplatelet therapy," said Professor P. Gabriel Steg, Principal Investigator of the LIBREXIA ACS trial, Hôpital Bichat, Paris, France.
Trial Discontinuation and Ongoing Studies
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 analyzed.
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 (搜索) 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."
Professor Tomasz Guzik, Chair of the ESC Congress Programme Committee, had highlighted the trial's significance ahead of its presentation: "For years, the field has awaited evidence whether factor XIa (搜索) inhibitors can reduce recurrent ischaemic events after acute coronary syndromes without the bleeding seen with earlier anticoagulants. This landmark trial could redefine the management of underlying risk after a myocardial infarction (搜索)."