Prospective, randomized trial of prolonged intracoronary urokinase infusion for chronic total occlusions in native coronary arteries

Objectives. The purpose of this study was to determine the safety and efficacy of three dosing regimens of intracoronary urokinase for facilitated angioplasty of chronic total native coronary artery occlusions. Background. Percutaneous transluminal coronary angioplasty of chronically occluded (>3 months) native coronary arteries is associated with low initial success secondary to an inability to pass the guide wire beyond the occlusion. Methods. Patients were enrolled if a chronic total occlusion >3 months old could not be crossed with standard angioplasty equipment. Of the 101 patients enrolled, 41 had successful guide wire passage and were excluded from urokinase treatment. The remaining 60 patients were randomized to receive one of three intracoronary dosing regimens of urokinase over 8 h (group A = 0.8 million U; group B = 1.6 million U; group C = 3.2 million U), and angioplasty was again attempted after completion of the urokinase infusion in 58 patients. Results. Coronary angioplasty was successful in 32 patients (53%) (group A 52%, group B 50%, group C 59%, p = 0.86). This study had a 90% power to detect at least a 50% difference between dosing groups at alpha 0.05. Bleeding complications requiring blood transfusion did not differ significantly among the dosing groups (A O%, B 15%, C 6%, p = 0.14), although major bleeding episodes were less common in group A (p < 0.05). There were no major procedural or in hospital complications. Angiographic follow-up in 69% of the patients with successful angioplasty revealed target vessel patency in 91% but an angiographic restenosis rate of 59%. Conclusions. A prolonged supraselective intracoronary infusion of urokinase can be safely administered and may facilitate angioplasty of chronic total occlusions. Lower doses of urokinase are equally effective and result in fewer bleeding complications than do higher dosage regimens. Vessel patency is frequently maintained, but restenosis remains a problem.