Coronary arterial thrombolysis with combined infusion of recombinant tissue-type plasminogen activator and urokinase in patients with acute myocardial infarction

Abstract

To determine whether tissue-type plasminogen activator (t-PA) and urokinase (UK) act synergistically to achieve coronary thrombolysis, incremental doses of both drugs were infused intravenously over 60 min. In 146 consecutive patients treated 3.0 ± 1.0 hr from symptom onset, coronary angiography was performed 90 min after the start of the infusion and at 7 days. The groups of patients treated by different dose regimen were as follows: group I, 14 patients treated with t-PA 25 mg and UK 0.5 million U; group II, 20 patients given t-PA 25 mg and UK 1.0 million U; group III, 24 patients given t-PA 1.0 mg/kg and UK 0.5 million U; group IV, 33 patients treated with t-PA 1.0 mg/kg and UK 1.0 million U; and group V, 55 patients given t-PA 1.0 mg/kg and UK 2.0 million U. In groups I and II, patency of the infarct-related vessel at 90 min was only 36% and 42%, respectively. With 1 mg/kg t-PA and increasing doses of UK (groups III to V), patency ranged from 72% to 75% (overall 73%). Repeat catheterization at 7 days demonstrated reocclusion in groups III to V in 10 of 110 (9%). The patency and reocclusion rates in groups III to V were not significantly different from those in our previous study of 386 patients treated with t-PA alone (150 mg over 6 to 8 hr). In that study the patency rate of the infarct-related vessel at 90 min was 75% (p = .66) and reocclusion occurred in 15% (p = .11). Patients in groups III to V who failed fibrinolytic therapy and underwent 'rescue' coronary angioplasty had a higher patency rate at follow-up (22 of 23, 96%) as compared with patients treated with t-PA alone (56 of 81, 69%; p = .017) and lower in-hospital mortality (0/27 vs 10/96, 10.4%; p = .075). We conclude that t-PA and urokinase do not act synergistically in achieving coronary thrombolysis and that 75% patency of the infarct-related vessel at 90 min may represent a plateau value for thrombolytic therapy. However, with the combined infusion of these agents, the bleeding frequency was not increased whereas the reocclusion rates were lower, particularly in patients who failed thrombolytic therapy and underwent emergency angioplasty.