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


METHODS
Systematic review and meta-analysis of prospective comparative trials.


METHODS
PubMed/MEDLINE database from 1966-October 2004.


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.


CONCLUSIONS
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.
Sander
Stephen
S
Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA. ccolema@harthosp.org
White
C Michael
CM
Coleman
Craig I
CI
D000671:Amputation, Surgical; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D006801:Humans; D016017:Odds Ratio; D010960:Plasminogen Activators / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use*
D011994:Recombinant Proteins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator