A double blind placebo controlled study of early and late administration of recombinant tissue plasminogen activator in acute myocardial infarction.

Within four hours of the onset of acute myocardial infarction 57 consecutive patients were randomised blindly to infusion of 150 mg recombinant tissue plasminogen activator (rt-PA) (group 1) over five hours or placebo (group 2) when they were first seen outside hospital or in the accident and emergency department. When they were admitted to the coronary care unit patients in group 1 also had placebo infused and those in group 2 were treated with rt-PA as well as placebo. Treatment with rt-PA started at a mean of 119 minutes (range 38-235) after the onset of pain in group 1 and 187 minutes (range 80-285) after the onset of pain in group. In 19 (79%) of 24 in group 1 and 16 of 25 (64%) in group 2 cardiac catheterisation 10-14 days after infarction showed thrombolysis in myocardial infarction grades 2 or 3. There was mean percentage shortening of the infarct related segments (Leighton method) of 16% in group 1 and 10.3% in group 2. For patients with anterior infarction mean percentage shortening was 20.5% in group 1 and 12.2% in group 2. Although there was no significant difference in global ejection fraction as assessed by contrast ventriculography or radionuclide ventriculography the infarct related regional third ejection fraction (a measure of the function of the territory of the affected coronary artery) was significantly improved by early treatment (41% group 1 and 28% group 2). Assessment of infarct size by the QRS scoring method of Palmeri showed QRS score less than or equal to 15/25 patients in group 1 and 8/27 in group 2. Nine patients developed 11 episodes of ventricular fibrillation; all patients in whom ventricular fibrillation developed during treatment with rt-PA were successfully resuscitated. There was no clinically significant bleeding. In seven (12%) patients clinical and electrocardiographic criteria suggested reocclusion. Five patients died from cardiac causes. Prehospital administration of rt-PA was feasible and significantly reduced the delay before thrombolysis was started. Earlier treatment improved myocardial function in the the infarct area and reduced the infarct size.