LIBREXIA ACS: Milvexian Fails to Reduce Recurrent CV Events After ACS
USA: Researchers have found in the phase III LIBREXIA ACS trial that the investigational factor XIa inhibitor milvexian did not reduce recurrent cardiovascular events when added to standard antiplatelet therapy in patients who had recently experienced an acute coronary syndrome (ACS).
Over a median follow-up of 12.2 months, cardiovascular death, myocardial infarction, or ischemic stroke occurred in 5.4% of patients receiving milvexian compared with 5.1% receiving placebo (hazard ratio, 1.05). Importantly, the treatment was not associated with increased major bleeding.
The findings, published in The New England Journal of Medicine by C. Michael Gibson, M.D., of the Baim Institute for Clinical Research, Boston, and colleagues, indicate that adding milvexian to antiplatelet therapy did not provide additional protection against major ischemic complications following ACS.
Patients remain vulnerable to recurrent ischemic events after an ACS episode, creating a need for secondary prevention approaches that can lower thrombotic risk without substantially increasing bleeding. Milvexian is an oral inhibitor of factor XIa, a component of the intrinsic coagulation pathway, and has been investigated as a potential option that could limit thrombosis while producing less bleeding than conventional anticoagulant strategies.
The randomized, placebo-controlled phase III trial enrolled 14,194 patients within seven days of an ACS event. Participants were randomly assigned to receive either oral milvexian at 25 mg twice daily or a matching placebo, alongside standard antiplatelet therapy.
The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or ischemic stroke, assessed using a time-to-event analysis. Investigators also evaluated Bleeding Academic Research Consortium (BARC) type 3c or 5 bleeding, which included intracranial or vision-threatening intraocular bleeding and fatal bleeding, as the principal safety outcome.
The key findings were as follows:
- Following a planned interim analysis of 556 adjudicated efficacy events, the trial was stopped early for futility.
- Of the 14,194 enrolled patients, 7,094 received milvexian and 7,100 received placebo.
- Over a median follow-up of 12.2 months, a primary efficacy event occurred in 384 patients (5.4%) in the milvexian group versus 365 patients (5.1%) in the placebo group.
- Milvexian did not significantly reduce recurrent cardiovascular events, with a hazard ratio of 1.05.
- BARC type 3c or 5 bleeding occurred in 23 patients (0.3%) receiving milvexian and 22 patients (0.3%) receiving placebo.
- There was no significant difference in major bleeding between the two groups.
The researchers concluded that although milvexian did not lower the risk of cardiovascular death, myocardial infarction, or ischemic stroke after ACS, it also did not increase intracranial or fatal bleeding. The results therefore temper expectations for factor XIa inhibition as an additional strategy for preventing recurrent cardiovascular events in patients already receiving antiplatelet therapy.
Reference:
DOI: 10.1056/NEJMoa2608717
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