Prourokinase for acute ischemic stroke: A meta-analysis of randomized controlled trials

Use of current thrombolytic agents, such as alteplase, is limited by risks such as intracranial hemorrhage, short half-life, and complex dosing regimens. These drawbacks hinder their optimal use in ischemic stroke treatment. Prourokinase (Pro-UK), with its fibrin specificity and favorable safety profile, offers a promising alternative. This meta-analysis aims to comprehensively evaluate its efficacy and safety in improving clinical outcomes for stroke patients.

A systematic literature review was conducted across PubMed, Scopus, and Web of Science from 1989 to 2024 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data analysis and visualization were performed using ReviewManager (RevMan) with a random-effects model. Risk of bias was assessed using the Cochrane tool, publication bias using Egger's test, and cumulative meta-analysis via trial sequential analysis.

A total of 5 randomized controlled trials comprising 3812 participants were included in this meta-analysis. The pooled analysis revealed that Pro-UK did not result in a statistically significant improvement in clinical outcomes among stroke patients, as measured by the National Institutes of Health Stroke Scale at 24 hours (mean difference = 0.06; 95% confidence interval [CI]: -0.09 to 0.21), the modified Rankin Scale (risk ratio [RR] = 0.99; 95% CI: 0.96-1.03), and the Barthel index (RR = 1.00; 95% CI: 0.99-1.01). Additionally, while there was a trend toward a reduction in systemic intracranial hemorrhage in the Pro-UK group, this finding did not reach statistical significance (RR = 0.86; 95% CI: 0.43-1.72).

While Pro-UK offers a theoretical advantage in reducing systemic bleeding due to its clot-specific action, current evidence does not significantly improve key clinical outcomes. The limited number and heterogeneity of existing randomized controlled trials underscore the need for more robust, large-scale trials to confirm its safety and efficacy in acute ischemic stroke.