Clinical experience with urokinase in intracoronary thrombolysis

A prospective nonrandomized study of the thrombolytic efficacy and dose-response effect of a high-molecular-weight urokinase, administered into the coronary artery, was conducted in 63 patients with acute myocardial infarction. Urokinase was infused (up to 180 min) at rates of 2000, 4000, 6000, and 10,000 IU/min in four consecutive groups of patients within 184 +/- 70 min following onset of chest pain. Of 54 patients with complete occlusion of the infarct-related vessel, 48 (89%) exhibited complete reperfusion. In 9 patients with incomplete occlusion, the degree of coronary stenosis was reduced with concomitant improvement in antegrade flow. The median effective dosage requirement of urokinase to reperfuse 50% of the treated patients was 180,000 IU. A relationship between the four infusion regimens and successful reperfusion was not found. The time to reperfusion, however, ranging from 42 +/- 30 to 60 +/- 41 min, appeared to be dose dependent. The reocclusion rate at follow-up (10-14 days) was 18%. Ejection fraction improved (40 +/- 8 vs. 47 +/- 8%, p = 0.002) in patients with low pretreatment values and in those treated within 2 h of the onset of symptoms. In-hospital mortality was 9%. Hemorrhage requiring transfusion occurred in 8% of the patients. None of the patients had levels of circulating fibrinogen inferior to 100 mg/dl. We conclude that urokinase can induce timely coronary reperfusion in patients with evolving myocardial infarction, at moderate infusion rates, and with concomitant induction of an only mild systemic lytic state.