Recombinant human prourokinase

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.

Acute ischemic stroke (AIS) requires timely thrombolysis to restore perfusion and minimize neurological damage. Recombinant human prourokinase (rhPro‐UK) has emerged as a promising alternative to alteplase, with potential efficacy and safety benefits within the critical 4.5‐h treatment window.

Electronic databases, including PubMed, ScienceDirect, and Cochrane Central, were comprehensively searched from inception until December 2024. Risk ratios (RRs) with 95% confidence intervals were pooled for the dichotomous outcomes using a random effects model in Review Manager software. The heterogeneity among the included trials was evaluated using the I2 statistics, and a sensitivity analysis was conducted to investigate the source of heterogeneity.

The final statistical analysis included 1179 participants in the rhPro‐UK and 1148 in the tPA group. Excellent functional outcome (modified Rankin Scale [mRS] 0‐1) (RR = 1.04, 95% CI: [0.98, 1.10]; p = 0.16) and good functional outcome (mRS 0‐2) (RR = 1.00, 95% CI: [0.96, 1.05]; p = 0.90; I2 = 0%) were comparable between the two groups. There was also no significant difference in mortality and major neurological improvement. However, there was a trend toward a lower risk of symptomatic intracranial hemorrhage (sICH) in the rhPro‐UK group (RR = 0.53, 95% CI: [0.18, 1.59]; p = 0.26).

rhPro‐UK demonstrated comparable efficacy to alteplase in achieving functional outcomes in AIS within 4.5 h, with no significant differences in mortality or neurological improvement. Although not statistically significant, a trend toward lower sICH risk with rhPro‐UK highlights its potential safety advantage. More high‐quality randomized clinical trials are required to confirm these findings.