Safety of thrombolytic therapy with urokinase or recombinant tissue plasminogen activator for peripheral arterial occlusion: a comprehensive compilation of published work.
OBJECTIVE
To report a comprehensive literature review focused on comparing the risk of complications with urokinase versus recombinant tissue plasminogen activator (rtPA) for thrombolytic treatment of peripheral arterial occlusions.


METHODS
The English-language literature between 1985 and 2002 was searched for studies that used tissue-derived urokinase or rtPA in the treatment of peripheral arterial occlusions. Forty-eight studies (22 urokinase, 22 rtPA, and 4 that included both treatments) were identified, encompassing 2226 urokinase-treated patients and 1927 rtPA-treated patients. The safety of each thrombolytic agent was assessed based on the incidence of major hemorrhage, intracerebral hemorrhage, major limb amputation, transfusions, and mortality.


RESULTS
The review revealed a wide range of study protocols, patient conditions, ages of occlusions, dosages/delivery methods of lytic agents, and criteria for reporting complications. The incidence of major hemorrhage varied widely, but the overall rate was lower among urokinase-treated patients (6.2%) than for patients treated with rtPA (8.4%, p=0.007). The overall incidence of intracerebral hemorrhage was also significantly lower for urokinase (0.4% versus 1.1% for rtPA, p=0.020). The major amputation rate was similar for both treatments (urokinase 7.9%, rtPA 7.2%), but the mortality rate was significantly lower for urokinase (3.0% versus 5.6% for rtPA, p<0.001). The need for transfusions was less frequent with urokinase (11.1% versus 16.1%, p=0.002).


CONCLUSIONS
These results from a large body of published literature suggest that urokinase may be associated with a lower incidence of complications than rtPA in the treatment of peripheral arterial occlusions.
Department of Vascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. ourielk@ccf.org
Kenneth
K
Ouriel
Krishna
K
Kandarpa
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000009:adverse effects*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*
D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator