Comparative safety and efficacy of urokinase and recombinant tissue plasminogen activator for peripheral arterial occlusion: A meta-analysis

Study Objective. To evaluate differences in the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and urokinase in the treatment of peripheral arterial occlusion. Design. Systematic review and meta-analysis of prospective comparative trials. Data Source. PubMed/MEDLINE database from 1966-October 2004. Measurements and Main Results. The literature was systematically searched to identify prospective comparative trials of urokinase and rt-PA for the treatment of peripheral arterial occlusion. The primary outcome measure was successful complete lysis of the occlusion. Other outcome measures were hemorrhage (major, minor, or combined), intracranial hemorrhage, limb loss, and mortality. Six trials were identified, five of which were randomized. On meta-analysis, the rate of clot lysis was higher With rt-PA than with urokinase (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.12-2.10, p = 0.007). However, urokinase was associated with lower rates of minor (OR 0.52, 95% CI 0.28-0.97, p = 0.04) and total (OR 0.51, 95% CI 0.29-0.91, p = 0.02) bleeding. Rates of major hemorrhage, intracranial hemorrhage, limb loss, and mortality were similar between agents. Conclusion. Urokinase was less effective than rt-PA in successfully lysing acute peripheral arterial occlusion, but it was associated with lower rates of total and minor bleeding. Overall, rt-PA was a reasonable substitute for urokinase, now that urokinase has been removed from the market in the United States. However, judicious monitoring for minor bleeding is necessary.