Comparative efficacy and safety between intravenous recombinant human prourokinase and alteplase in acute ischemic stroke treatment: a meta-analysis of randomized controlled trials

BACKGROUND: Recombinant human prourokinase (rhPro-UK) has been investigated as an alternative thrombolytic agent to alteplase for acute ischemic stroke (AIS). While alteplase remains the standard of care, uncertainties persist regarding whether rhPro-UK provides similar efficacy and safety outcomes. This systematic review and meta-analysis aimed to compare intravenous rhPro-UK with alteplase in patients with AIS. METHODS: A systematic literature search was conducted in PubMed, Embase, and Cochrane Central up to January 2025. Randomized controlled trials (RCTs) comparing intravenous rhPro-UK with alteplase were included. Outcomes of interest were functional recovery (modified Rankin Scale [mRS] 0-1 and 0-2 at 90 days), early neurological improvement (National Institutes of Health Stroke Scale [NIHSS] reduction within 24 hours), intracranial hemorrhage, all-cause mortality, and recurrent stroke. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under a random-effects model. Risk of bias was assessed with the Cochrane RoB 2 tool. RESULTS: Three RCTs involving 2295 patients were included (1209 treated with rhPro-UK; 1148 with alteplase). No statistically significant differences were observed between groups for intracranial hemorrhage (OR 1.04; 95% CI: 0.73-1.48), mRS 0-1 at 90 days (OR 0.91; 95% CI: 0.77-1.08), mRS 0-2 at 90 days (OR 0.95; 95% CI: 0.79-1.14), early NIHSS improvement (OR 0.94; 95% CI: 0.79-1.11), all-cause mortality (OR 1.16; 95% CI: 0.66-2.03), or recurrent stroke (OR 0.72; 95% CI: 0.31-1.66). CONCLUSIONS: Intravenous rhPro-UK demonstrated comparable efficacy and safety to alteplase in AIS, supporting its role as a potential alternative thrombolytic, particularly in regions with limited access to alteplase.