Safety and Efficacy of Asundexian in Cardiovascular Diseases, Updated Systemic Review and Meta Analysis

Background: Thromboembolic events remain a major cause of morbidity and mortality in cardiovascular diseases. Asundexian, an oral factor XIa inhibitor, has been proposed to reduce thrombosis while minimizing bleeding risk. The recent OCEANIC-STROKE trial provided substantial new evidence. We conducted an updated systematic review and meta-analysis incorporating this large trial. Methods: PubMed, Scopus, embase and CENTRAL were searched through April 2026. Five RCTs (n=31,301) comparing asundexian 50 mg daily with placebo or apixaban in patients with AF, acute myocardial infarction or stroke were included. Outcomes included all-cause mortality, ischemic stroke, stroke or systemic embolism, ISTH-defined major bleeding, other bleeding events, adverse events (AEs) and serious AEs. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Five RCTs involving 31,301 participants were included. Asundexian did not significantly affect all-cause mortality (RR 0.98, 95% CI 0.85–1.14), ischemic stroke (RR 1.33, 95% CI 0.66–2.66) or stroke/systemic embolism (RR 1.20, 95% CI 0.28–5.12). No significant differences were observed in major bleeding, clinically relevant non-major bleeding, minor bleeding, hemorrhagic stroke, adverse events or serious adverse events. Sensitivity analyses reduced heterogeneity and suggested a lower risk of stroke/systemic embolism (RR 0.74, 95% CI 0.65–0.84), while other findings remained unchanged. Conclusions: Asundexian demonstrated a favorable safety profile but did not significantly reduce mortality or ischemic stroke. Sensitivity analyses suggest a potential benefit in reducing stroke or systemic embolism without increasing bleeding risk. Further trials are needed to identify patient populations most likely to benefit.