Lessons from the European Cooperative recombinant tissue-type plasminogen activator (rt-PA) versus placebo trial

AbstractA new European Cooperative Study Group trial of 721 patients has recently found recombinant tissue-type plasminogen activator (rt-PA) to positively affect infarct size, ten ventricular function, cardiovascular morbidity and early survival. In this 26 center trial, patients were randomized to receive either placebo or 100 mg rt-PA intravenously over 3 h. Heparin (5,000 U bolus injection and then 1,000 U/h) and aspirin (250 mg initially, then 75 to 125 mg every other day) were given to all patients until angiography was performed (10 to 22 days after allocation).Enzymatic infarct size was found to be 20% smaller in the rt-PA group (2p = 0.0018) than in the control group. At angiography, 83% of rt-PA-treated patients had a patent infarct-relaled vessel compared with 77% of the placebotreated patients. Ejection fraction was 2.2% points higher (2p = 0.04) and end-diastolic and end-systolic volumes were ± 6 ml smaller (2p = 0.003) than in the control group, indicating an improved left ventricular pump function in the thrombolysis group. Cardiovascular complications such as shock, ventricular fibrillation and pericarditis were markedly fewer in patients treated with rt-PA, but bleeding complications occurred more frequently. An intracranial hemorrhage within 3 days after the infusion of rt-PA was observed in five patients (1.4%). None of these bleeding episodes was causally related to death. Although this European Cooperative trial was not designed primarily as a mortality study, important reductions in early mortality rates were observed. At 14 days, the death rate among rt-PA-treatcd patients was 2.8%, which is 51% (95% confidence interval −76% to +1%, 2p = 0.053) lower than the 5.7% mortality rate of the control group. At 3 months, the mortality rate was 5.1% in the rt-PA group, which is 36% (95% confidence interval −63% to +13%, 2p = 0.121) lower than the 7.9% in the control group. In patients treated within 3 h of symptoms, the European Cooperative Study Group reported mortality reductions of 82% (95% confidence interval −95% to −31%, 2p = 0.009) at 14 days and 59% (95% confidence interval −83% to −2%, 2p = 0.045) at 3 months. The early mortality rates observed in this trial were very similar to those reported previously by the same European Cooperative Study Group for a similarly selected and treated group of patients and are the lowest so far published in large trials with intravenously administered thrombolytic agents.The results of these European multicenter trials, together with the recent findings of large studies conducted in the United States (Johns Hopkins Hospital trial, Thrombolysis and Angioplasty in Myocardial Infarction [TAMI], Thrombolysis in Myocardial Infarction [TIMI]), further add to evidence that early thrombolytic treatment with rt-PA in addition to antithrombotic and antiplatelet medication is of major benefit for patients with an acute myocardial infarction