Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide. Recombinant human prourokinase (rhPro-UK) has emerged as a promising thrombolytic agent amid the global shortage of thrombolytics. We assessed the safety and efficacy of rhPro-UK in AIS patients within 4.5 h of stroke onset through a systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, and Cochrane until January 2024. Data were pooled using risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) in R version 4.3. PROSPERO ID: CRD42025638980. Three RCTs (2289 patients) were included. rhPro-UK showed comparable efficacy to recombinant tissue plasminogen activator (r-tPA) in excellent neurological recovery (mRS 0-1: RR 1.04, 95% CI [0.98, 1.10], P = 0.19) and functional independence (mRS 0-2: RR 1.00, 95% CI [0.96, 1.05], P = 0.87). However, rhPro-UK significantly reduced NIHSS scores at 24 h (MD -0.43, 95% CI [-0.85, -0.02], P = 0.04) and seven days (MD -0.85, 95% CI [-1.39, -0.30], P < 0.01), and decreased systemic bleeding (RR 0.60, 95% CI [0.49, 0.75], P < 0.01). No significant differences were observed in 90-day mortality (RR 1.13, 95% CI [0.62, 2.05], P = 0.69) or intracerebral hemorrhage (RR 0.83, 95% CI [0.61, 1.13], P = 0.23). rhPro-UK demonstrates comparable efficacy to r-tPA with reduced NIHSS scores and systemic bleeding, supporting its role as a cost-effective and safer alternative for AIS treatment within 4.5 h. Further investigation in stroke management protocols is warranted.