LIBREXIA ACS Fails to Improve Cardiovascular Outcomes, Doesn’t Increase Bleeding Risk

Despite failing to reduce cardiovascular events after acute coronary syndrome (ACS), milvexian did show no difference in bleeding compared to placebo in the LIBREXIA ACS trial.¹

Presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Philippe Gabriel Steg, MD, a professor of cardiology at the Université Paris and chief of the department of cardiology and director of the coronary care unit at Hôpital Bichat, these full data recontextualize LIBREXIA ACS’s failure and early termination in reference to the ongoing LIBREXIA-AF and LIBREXIA-Stroke trials.¹

“Now, why is this still important despite the neutral results from the main trial? Because this compound is being tested in 2 other conditions with 2 other large-scale ongoing trials, one in atrial fibrillation at a different dose, and the other in secondary stroke prevention,” Steg told HCPLive in an exclusive interview. “These 2 trials are ongoing and will report next year, so stay tuned.”

LIBREXIA’s Structure

LIBREXIA ACS was a phase 3, randomized, double-blind, placebo-controlled, event-driven study conducted across 1003 locations worldwide. Eligible patients had ≥2 risk factors from among age ≥65 years, diabetes mellitus, prior myocardial infarction, multivessel coronary artery disease, coronary artery bypass graft surgery, and peripheral artery disease, among others, and were required to have an index event meeting all 3 of the following criteria:

• Clinical syndrome consistent with spontaneous cardiac ischemia
• Diagnosis of ACS
• Cardiac biomarker elevation²

Patients were randomly assigned in a 1:1 ratio to receive either oral milvexian 35 mg or placebo, both administered twice a day. The primary endpoint was time to first occurrence of major adverse cardiovascular event (MACE) during a time frame of ≤3 years and 6 months. Secondary endpoints included time to first occurrence of major adverse vascular event, time to first occurrence of composite of all-cause mortality, myocardial infarction, and ischemic stroke, and others.²

Termination and Analysis

A total of 14,194 patients were enrolled at 893 sites across 44 countries; however, the Independent Data Monitoring Committee recommended discontinuing the trial after a preplanned interim analysis revealed its low likelihood of achieving its primary endpoint. After a median follow-up of 10 months, the primary efficacy endpoint had occurred at a similar incidence in both groups: 5.4% of patients receiving milvexian and 5.1% of patients receiving placebo (HR, 1.05; 95% CI, 0.91-1.21; P = .5). This analysis proved the futility of the trial.¹

Steg and colleagues observed no difference with milvexian for the individual components of the primary endpoint or any secondary efficacy endpoints. However, there was also no difference in the principal safety endpoint of intracranial or fatal bleeding. This occurred in 0.3% of patients with milvexian and placebo (HR, 1.04; 95% CI, 0.58-1.87; P = .88).¹

Ultimately, Steg and colleagues concluded that, despite the trial’s failure, its impact on bleeding risk establish it as a safe therapeutic option for this population. The ongoing LIBREXIA-AF and LIBREXIA STROKE trials are aiming to reflect this evidence in other disease states.¹

“The stroke trial is going against placebo on top of standard antiplatelet therapy, and so we’re hoping to see additional efficacy with minimal bleeding,” Steg said. “The AF trial is going against an established therapy, apixaban full dose, and here what we’re hoping to see is a marked reduction in bleeding and similar efficacy.”

Editors’ Note: Steg reports disclosures with Amgen, AstraZeneca, Boehringer-Ingelheim, Janssen, Lilly, Merck, and others.

References

1. Steg P. LIBREXIA ACS: Milvexian after recent ACS. Presented at the European Society of Cardiology Congress 2026, Munich, Germany. August 28-31, 2026.

2. Janssen Research & Development, LLC. A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome (LIBREXIA-ACS). ClinicalTrials.gov Identifier: NCT05754957. Updated July 6, 2026. Accessed August 28, 2026. https://clinicaltrials.gov/study/NCT05754957