Combination of urokinase and alteplase in the treatment of myocardial infarction

The objective of this multicenter open-label study was to evaluate the efficacy and safety of the simultaneous intravenous administration of urokinase and alteplase infused over 60 minutes in patients with acute myocardial infarction. In 129 analyzable patients treated within 6 hours of symptom onset, coronary angiography was performed 90 minutes after the start of the infusion (127 patients) and again at 7 to 10 days (119 patients). Coronary angiograms were analyzed by a core laboratory in a blinded fashion. Patients were consecutively enrolled into five treatment groups: Group I (25 patients) received alteplase, 20 mg, and urokinase, 2.0 mU; Group II (27 patients) received alteplase, 40 mg, and urokinase, 1.0 mU; Group III (28 patients) received alteplase, 50 mg, and urokinase, 1.0 mU; Group IV (25 patients) received alteplase, 50 mg, and urokinase, 2.0 mU; Group V (27 patients) received alteplase, 1 mg/kg, and urokinase, 1.0 mU. Aspirin and heparin were given to all patients. Patency rates of the infarct-related artery at 90 minutes after start of thrombolytic treatment were 63% (Group I), 80% (Group II), 75% (Group III), 71% (Group IV), and 65% (Group V). The patency of the infarct-related artery at 90 minutes did not differ significantly between treatment groups (P=0.662). Patency rates at the follow-up evaluation were 88%, 83%, 96%, 85%, and 92% in Groups I to V, respectively (P=0.494). The patency rates achieved by the combined administration of urokinase and alteplase in the doses employed in this study are high but do not appear to be superior to those obtained with the recommended dose of each drug alone and the reocclusion rates seem to be low. The combination therapy in this pilot trial appears to be safe and associated with a low in-hospital mortality.