Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase.

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.