Key result
Oral FXIa inhibitors cut recurrent ischemic stroke ~29% vs placebo without excess major bleeding.
Why the study?
Factor XIa inhibitors may provide effective thromboprophylaxis with less bleeding liability than conventional anticoagulants. This study evaluated their efficacy and safety in patients with acute noncardioembolic ischemic stroke or high-risk TIA.
Do oral Factor XIa inhibitors reduce recurrent symptomatic ischemic stroke compared with placebo in adults with acute noncardioembolic ischemic stroke or high-risk TIA receiving antiplatelet therapy?
Meta-Analysis (n=16,501)
Do oral Factor XIa inhibitors reduce recurrent symptomatic ischemic stroke compared with placebo in adults with acute noncardioembolic ischemic stroke or high-risk TIA receiving antiplatelet therapy?
Answers are grounded in this paper and cite their sources.
In patients with acute noncardioembolic ischemic stroke or high-risk TIA on antiplatelet therapy, adding oral FXIa inhibitors significantly reduces recurrent and disabling/fatal strokes without significantly increasing major bleeding.
Background: Factor XIa (FXIa) inhibitors may provide effective thromboprophylaxis with less bleeding liability than conventional anticoagulants. We evaluated the efficacy and safety of FXIa inhibitors in patients with acute non cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA). Methods: A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Cochrane databases up to May 2026. We performed a meta-analysis of randomized controlled trials comparing oral FXIa inhibitors (Asundexian or Milvexian) with placebo on a background of antiplatelet therapy in adults randomized within 48-72 hours of symptom onset. The primary efficacy outcome was recurrent symptomatic ischemic stroke. Individual patient data (IPD) were reconstructed from Kaplan-Meier curves using the "IPDfromKM" R package. A random-effects meta-analysis was performed with R software to calculate risk ratios (RR), hazard ratios (HR), and mean differences (MD), all with 95% confidence intervals (CIs). Results: Three trials involving 16,501 reconstructed patient records (9,189 FXIa inhibitor; 7,312 placebo). FXIa inhibition significantly reduced recurrent symptomatic ischemic stroke compared with placebo (HR 0.71, 95% CI 0.61-0.82; p<0.001). FXIa inhibitors were also associated with lower risks of any stroke (RR 0.75, 95% CI 0.67-0.85; p<0.0001) and disabling or fatal stroke (RR 0.70, 95% CI 0.57-0.88; p=0.001). Rates of major bleeding (RR 1.14, 95% CI 0.89-1.45), clinically relevant non-major bleeding, all-cause mortality, cardiovascular mortality, adverse events, and serious adverse events did not differ significantly between groups. Conclusions: Among patients with acute non cardioembolic ischemic stroke or high-risk TIA receiving antiplatelet therapy, FXIa inhibitors significantly reduce recurrent ischemic stroke and disabling or fatal stroke without increasing major bleeding, supporting their potential role in secondary stroke prevention.
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Emara et al. (2026) conducted a meta-analysis in Acute noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) (n=16,501). Oral Factor XIa (FXIa) inhibitors (asundexian or milvexian) vs. Placebo on a background of antiplatelet therapy was evaluated on Recurrent symptomatic ischemic stroke (HR 0.71, 95% CI 0.61-0.82, p=<0.001). Oral FXIa inhibitors reduced recurrent symptomatic ischemic stroke vs placebo on background antiplatelet therapy without increasing major bleeding.
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