Intravenous recombinant human prourokinase for acute ischemic stroke: a network meta-analysis

INTRODUCTION: Acute ischemic stroke (AIS) requires prompt thrombolytic therapy to restore cerebral perfusion. Recombinant human prourokinase (rhPro-UK) has emerged as a potential alternative to standard agents, but the optimal dosage remains unclear. EVIDENCE ACQUISITION: A systematic review and network meta-analysis was conducted using PubMed and Embase up to January 27, 2025. Eligible studies were randomized controlled trials (RCTs) comparing intravenous rhPro-UK dosages in adults with AIS. Outcomes included changes in NIHSS scores (24 hours and 7 days), mRS scores (0-1 and 0-2), all-cause mortality, serious adverse events (SAEs), and symptomatic intracranial hemorrhage (SIH). Data were analyzed using a Bayesian random-effects model in R (v4.4.2), with results reported as mean differences (MDs), odds ratios (ORs), and risk differences (RDs) with 95% confidence intervals (CIs). EVIDENCE SYNTHESIS: Eight RCTs (N.=4309; mean age 64.7 years; 33.1% female) were included. Both 35 mg and 50 mg rhPro-UK improved NIHSS scores at 24 hours (MD: -1.03 and -0.44) and 7 days (MD: -1.19 and -0.86) versus standard care. The combination of 40 mg rhPro-UK + alteplase (ALT) showed the highest probability of achieving mRS 0-2 (OR: 1.59). The 50 mg dose was associated with increased mortality (OR: 2.34), while the 35 mg dose had the highest estimated SIH risk (OR: 4.73). CONCLUSIONS: Both 35 mg and 50 mg rhPro-UK improve early neurological outcomes. However, 40 mg rhPro-UK + ALT may offer the most favorable efficacy-safety profile. Further trials are warranted to optimize dosing strategies.