Comparative efficacy and safety of prourokinase versus alteplase for acute ischemic stroke within 4.5 hours: a systematic review and meta-analysis of randomized controlled trials

Intravenous thrombolysis with recombinant tissue plasminogen activator, such as alteplase, is the standard treatment for acute ischemic stroke (AIS). However, concerns about cost and safety have led to an interest in alternative thrombolytics like prourokinase (rhPro-UK). This meta-analysis evaluated the efficacy and safety of prourokinase compared to alteplase for AIS treatment within 4.5 hours of symptom onset. A literature search was conducted across PubMed, Web of Science, and Scopus up to January 2025. The outcome measures included functional outcomes (modified Rankin Scale [mRS]), early neurological improvement (NIHSS reduction), and safety outcomes, involving symptomatic intracranial hemorrhage (sICH). PROSPERO registration is CRD42025632210. Three RCTs with a total of 2,289 patients were included. The proportion of patients achieving excellent functional outcomes (mRS 0-1 at 90 days) did not differ significantly between groups (risk ratio (RR): 1.04, 95% confidence interval (CI): 0.98-1.10, p = 0.17). Similarly, good functional outcomes (mRS 0-2) were comparable (p = 0.86). Early neurological improvement at 24 hours was also similar (p = 0.32). However, prourokinase showed a slight but statistically significant advantage in NIHSS score reduction at 24 hours (mean difference (MD): -0.43, 95% CI: -0.85 to -0.02, p = 0.04). The risk of sICH, defined by ECASS III (p = 0.16) and SITS-MOST (p = 0.07), showed insignificant difference. Prourokinase is a safe and effective thrombolytic agent for AIS within 4.5 hours, demonstrating non-inferiority to alteplase in both efficacy and safety. Its advantages, including lower cost and ease of administration, make it a viable alternative. Future large-scale trials are recommended.