A Phase 3, Randomized, Double-blind, Placebo-controlled, Event-driven Study to Demonstrate the Efficacy and Safety of Milvexian, an Oral Factor XIa Inhibitor, After a Recent Acute Coronary Syndrome (Librexia ACS)

doi:10.1056/nejmoa2608717

LIBREXIA ACS

Patient / Population Intervention / Exposure Comparison Outcome

In 14,194 patients with a recent acute coronary syndrome, milvexian added to antiplatelet therapy did not reduce cardiovascular death, myocardial infarction or ischaemic stroke compared with placebo.

N

14,194patients

Design

International, multicentre, randomised, double-blind (quadruple-masked), placebo-controlled, event-driven phase 3 trial; 1:1 allocation to milvexian or matched placebo on top of investigator-chosen standard antiplatelet therapy (SAPT or DAPT); randomisation stratified by planned type and duration of antiplatelet therapy; follow-up planned until 875 primary-endpoint events (up to about 3.5 years)

Endpoint

Time to first occurrence of the composite of cardiovascular death, myocardial infarction or ischaemic stroke

Relevance

2Important — one of several pillars.

ResultCardiovascular death, myocardial infarction or ischaemic stroke 5.4% vs 5.1% over a median 10 months (HR 1.05, 95% CI 0.91-1.21; P = 0.50). Intracranial or fatal bleeding (BARC 3c or 5) 0.3% in both arms (HR 1.04, 95% CI 0.58-1.87; P = 0.88). Stopped for futility at the interim analysis in November 2025.

Gibson CM, Steg PG, Bahit MC, et al. N Engl J Med. 2026; published online 29 August. 10.1056/nejmoa2608717

Discussion & critique

Factor XI inhibition promised the separation every antithrombotic programme is chasing — fewer events without more bleeding. In 14,194 patients after an acute coronary syndrome, milvexian delivered the second half and none of the first: identical bleeding, identical events, stopped for futility. The bleeding safety is real and matters for the atrial fibrillation and stroke programmes still running, but on top of modern antiplatelet therapy after ACS there was nothing left to prevent.