Abstract Body: Background: Several studies have shown that tranexamic acid (TXA), an anti-fibrinolytic agent, may reduce hematoma expansion (HE) in intracerebral hemorrhage (ICH), but its therapeutic time window is unclear. We analyzed the efficacy and safety of TXA based on its time of administration after hemorrhage onset.

Methods: We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) published up to July 27, 2024 comparing TXA with placebo in ICH. We excluded trials that used TXA for longer than 3 days which causes delayed vasospasm, increasing the risk of cerebral ischemia. The primary outcomes were HE, 24-hour hemorrhagic volume change, 90-day mortality and poor functional outcome. We grouped the trials into 2 hours, 8 hours or 24 hours of TXA administration after hemorrhage onset. We pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) using Rstudio. Heterogeneity was examined with the I2 test.

Results: We included 12 studies with 3,567 patients. Most of the studies used 1 g TXA in patients with Glasgow Coma Scale score ranging from 13-15. TXA reduced HE risk (OR 0.85; 95% CI 0.73 to 0.98; p= 0.03; I2= 0%). This reduction was observed in studies that administered TXA within 8 hours of ICH onset (OR 0.82; 95% CI 0.70 to 0.97; p= 0.02; I2= 0%). TXA slightly reduced 24-hour hemorrhagic volume (MD -1.30 mL; 95% CI -2.51; -0.09; p= 0.04; I2= 47%). This reduction was mainly seen in patients who were administered TXA within 8 hours of hemorrhage onset (MD -1.86 mL; 95% CI -3.15 to -0.58; p< 0.01; I2= 35%). There were no significant differences in poor functional outcome (OR 0.87; 95% CI 0.67 to 1.15; p= 0.34; I2= 24%), 90-day mortality (OR 1.00; 95% CI 0.84 to 1.19; p= 0.96; I2= 0%), major thromboembolic events (OR 1.22; 95% CI 0.82 to 1.82; p= 0.33; I2= 0%), neurosurgical intervention (OR 0.94; 95% CI 0.61-1.45; p= 0.78; I2= 0%) or length of hospital stay (MD -0.49 days; 95% CI -3.27 to 2.29; p= 0.73; I2= 0%).

Conclusion: TXA reduced the risk of HE and slightly reduced 24-hour hemorrhagic volume in patients with ICH within 8 hours. Larger RCTs stratifying administration timing are required to establish these findings.