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

A new European Cooperative Study Group trial of 721 patients has recently found recombinant tissue-type plasminogen activator (rt-PA) to positively affect infarct size, left 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-related vessel compared with 77% of the placebo-treated 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.(ABSTRACT TRUNCATED AT 250 WORDS)