Milvexian Added to Antiplatelet Therapy Did Not Reduce Ischemic Events After Acute Coronary Syndrome

Treatment with milvexian (Johnson & Johnson, Beerse, Belgium; Bristol Myers Squibb, New York, NY), an investigational oral factor XIa inhibitor, did not reduce the risk of cardiovascular death, myocardial infarction, or ischemic stroke when added to standard antiplatelet therapy in people with recent acute coronary syndrome, according to data published in The New England Journal of Medicine.

In LIBREXIA ACS, a randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT05754957), treatment with milvexian was evaluated in adults enrolled within 7 days after an acute coronary syndrome event, including ST-segment elevation myocardial infarction, type 1 non–ST-segment elevation myocardial infarction, or unstable angina with cardiac biomarker positivity. Participants were randomly assigned 1:1 to receive milvexian 25 mg twice daily or placebo, in addition to investigator-selected standard antiplatelet therapy.

The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The principal safety outcome was Bleeding Academic Research Consortium type 3c or 5 bleeding, defined as intracranial bleeding, intraocular bleeding that compromises vision, or fatal bleeding.

Trial Results

• The trial enrolled 14,194 participants across 893 sites in 44 countries before it was stopped for futility after a prespecified interim analysis.
• A total of 7094 participants were assigned to milvexian and 7100 were assigned to placebo.
• After a median follow-up of 12.2 months, the primary efficacy outcome occurred in 384 participants (5.4%) in the milvexian group and 365 participants (5.1%) in the placebo group (hazard ratio [HR], 1.05; 95% CI, 0.91 to 1.21; P=.50).
• Cardiovascular death occurred in 110 participants (1.6%) treated with milvexian and 112 participants (1.6%) treated with placebo (HR, 0.98; 95% CI, 0.75 to 1.28).
• Myocardial infarction occurred in 249 participants (3.5%) in the milvexian group and 236 participants (3.3%) in the placebo group (HR, 1.05; 95% CI, 0.88 to 1.26).
• Ischemic stroke occurred in 60 participants (0.8%) treated with milvexian and 46 participants (0.6%) treated with placebo (HR, 1.30; 95% CI, 0.89 to 1.91).
• BARC type 3c or 5 bleeding occurred in 23 participants (0.3%) in the milvexian group and 22 participants (0.3%) in the placebo group (HR, 1.04; 95% CI, 0.58 to 1.87; P=.88).
• Clinically relevant nonmajor bleeding occurred in 363 participants (5.2%) treated with milvexian and 318 participants (4.5%) treated with placebo (HR, 1.14; 95% CI, 0.98 to 1.33).

Potential Implications for Neurologic Practice

In this trial, adding milvexian to antiplatelet therapy after acute coronary syndrome did not impact ischemic stroke risk or the broader composite ischemic outcome. The results may help contextualize ongoing factor XIa inhibitor research in cerebrovascular disease. The authors noted that factor XIa inhibition may have different effects across vascular beds, with prior data suggesting greater promise in stroke populations than in people after acute coronary syndrome. Milvexian is being evaluated separately in the LIBREXIA Stroke trial among people after acute ischemic stroke or high-risk transient ischemic attack.

Source

Gibson CM, Steg PG, Bahit MC, et al; LIBREXIA ACS Committees and Investigators. Milvexian with antiplatelet therapy after acute coronary syndrome event. N Engl J Med. Published online August 29, 2026. doi:10.1056/NEJMoa2608717