Sequential combination thrombolytic therapy for acute myocardial infarction: results of the pro-urokinase and t-P enhancement of thrombolysis (PATENT) trial

Objectives. The present study was designed to test the efficacy and safety of sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction. Background. Efforts continue to identify thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-P and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As result, certain combinations of these activators have been found to be synergistic in vitro and in vivo. Methods. In multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and gives low dose bolus of rt-P (5 to 10 mg) followed by 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min. Results. Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect possible reocclusion. All 28 patients with patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death. Conclusions. sequential combination of low dose rt-P and reduced-dose pro-urokinase produced high TIMI 3 patency rate, was well tolerated and was associated with low reocclusion rate.