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LIBREXIA ACSAcute Coronary SyndromesNew England Journal of Medicine
Efficacy and Safety of Milvexian Added to Antiplatelet Therapy after Acute Coronary Syndrome
Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event
View Full PaperWhy the trial?
Adding an anticoagulant to antiplatelet therapy after acute coronary syndrome reduces ischaemic events but has been limited by bleeding. Factor XIa inhibition promises antithrombotic protection with less bleeding, and LIBREXIA ACS asked whether milvexian delivers that benefit after a recent ACS.
Does milvexian reduce the risk of cardiovascular death, myocardial infarction, or ischemic stroke in patients with a recent acute coronary syndrome event?
Population
14,194 patients within 7 days of an acute coronary syndrome event
Comparison
Milvexian 25 mg twice daily vs matched placebo, added to standard antiplatelets
Design
Phase 3 randomized placebo-controlled trial; terminated early for futility
Follow-up
Median 12.2 months
Key result
Milvexian added to standard antiplatelet therapy did not decrease the risk of cardiovascular death, myocardial infarction, or ischemic stroke compared with placebo (HR 1.05; 95% CI 0.91-1.21; P=0.50).
Authors
Discussion
Key questions
Member takes
Where experts stand
Experts uniformly read LIBREXIA ACS as a clear null result for milvexian after ACS, with the factor XIa hypothesis failing to deliver efficacy in this setting, though the clean safety profile keeps interest alive for other indications.
Cardiologists agree that adding milvexian to antiplatelet therapy after acute coronary syndromes produced no ischemic benefit and the trial was stopped for futility. The safety signal was reassuringly clean, but no one frames this as practice-relevant. The open question is whether factor XIa inhibition can still prove itself at higher doses or in different populations such as atrial fibrillation or secondary stroke prevention.
Agreement
Multiple clinicians converge on the same bottom line: milvexian showed no efficacy benefit after ACS while maintaining a favorable bleeding profile, meaning factor XIa inhibition at this dose adds nothing to contemporary antiplatelet therapy.
5 clinicians say this directly
What they’re arguing about
supportiveneutralcautiouscritical
Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.
Still unclear
Whether higher doses of milvexian can deliver efficacy in other thrombotic settings remains untested in phase 3. The ongoing atrial fibrillation and secondary stroke prevention trials use different doses and populations, and experts have not yet weighed in on whether this ACS failure should temper expectations for those programs.
Key expert perspectives
The factor XIa hypothesis falls short after ACS and the unmet need remains
Galluzzo stated that milvexian 25 mg BID added to antiplatelet therapy did not reduce CV death, MI, or ischaemic stroke (HR 1.05) and did not increase BARC 3c/5 bleeding. He concluded the unmet need remains.
Distilled from their postX post
Residual ischemic risk after ACS persists and milvexian does not address it
Damluji noted patients remain at high risk for recurrent ischemic events despite dual antiplatelet therapy, high-intensity statins, and current-generation stents. He highlighted the trial tested adding an oral factor XIa inhibitor to that regimen and shared key points for clinical practice and market implications.
The Factor XIa hypothesis did not deliver efficacy in ACS
Gouda framed milvexian as aiming to reduce thrombosis with less impact on normal hemostasis, then reported it did not reduce CV death, MI, or ischemic stroke after ACS (HR 1.05, p=0.50). He concluded the Factor XIa hypothesis did not deliver efficacy here.
Overview
Milvexian adds no ischemic benefit after ACS; safety supports continued evaluation in ongoing atrial fibrillation and stroke prevention trials.
Key Points
- To evaluate the efficacy and safety of adding the oral factor XIa inhibitor milvexian to standard antiplatelet therapy in patients with a recent acute coronary syndrome event.
- Phase 3, randomized, placebo-controlled trial (NCT05754957) enrolling 14,194 patients within 7 days after an acute coronary syndrome event.
- Patients were assigned in a 1:1 ratio to receive oral milvexian (25 mg twice daily, n=7,094) or matched placebo (n=7,100) on top of standard antiplatelet therapy, with a median follow-up of 12.2 months.
- The primary efficacy outcome (cardiovascular death, myocardial infarction, or ischemic stroke) occurred in 384 patients (5.4%) in the milvexian group and 365 patients (5.1%) in the placebo group (HR, 1.05; 95% CI, 0.91 to 1.21; P=0.50), leading to early trial termination for futility.
- Principal safety endpoint of BARC type 3c or 5 bleeding occurred in 23 patients (0.3%) in the milvexian group and 22 patients (0.3%) in the placebo group (P=0.88).
Evidence details
What drove the result?
| Outcome | Milvexian | Placebo |
|---|---|---|
| CV death, MI, or ischemic stroke | 384 (5.4%) | 365 (5.1%) |
| HR 1.05 (95% CI 0.91-1.21); P=0.50 - trial stopped for futility at interim | ||
Limitations & tradeoffs
Safety
BARC 3c or 5 bleeding (intracranial/fatal) 23/7094 (0.3%) vs 22/7100 (0.3%); P=0.88.
Statistical certainty
terminated for futility at a planned interim based on 556 adjudicated events.
Design limitations
median follow-up of 12.2 months is relatively short, and only one dose (25 mg twice daily) was evaluated.
Structured PICO
Does milvexian reduce the risk of cardiovascular death, myocardial infarction, or ischemic stroke in patients with a recent acute coronary syndrome event?
P
Population
14,194 patients with a recent acute coronary syndrome event, followed for a median of 12.2 months.
I
Intervention
Oral milvexian (25 mg twice daily) added to standard antiplatelet therapy
C
Comparator
Matched placebo added to standard antiplatelet therapy
O
Outcome
Composite of cardiovascular death, myocardial infarction, or ischemic stroke as evaluated in a time-to-event analysiscomposite
In patients with recent acute coronary syndrome, adding the factor XIa inhibitor milvexian to standard antiplatelet therapy did not reduce ischemic events, leading to early termination for futility.
Main Result
Hazard Ratio: 1.05 (95% CI 0.91–1.21)
Absolute Event Rate: 5.4% vs 5.1%
p-value: p=0.50
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Gibson et al. (2026) conducted an RCT in Acute coronary syndrome (n=14,194). Milvexian vs. Placebo was evaluated on Composite of cardiovascular death, myocardial infarction, or ischemic stroke (HR 1.05, 95% CI 0.91-1.21, p=0.50). Milvexian added to standard antiplatelet therapy did not decrease the risk of cardiovascular death, myocardial infarction, or ischemic stroke compared with placebo (HR 1.05; 95% CI 0.91-1.21; P=0.50).