A Prospective Trial of Intravenous Streptokinase in Acute Myocardial Infarction (I.S.A.M.)

Within six hours after the onset of symptoms of myocardial infarction, we randomly assigned 1741 patients up to 75 years of age to a one-hour intravenous infusion of 1.5 million IU of streptokinase or placebo. At 21 days mortality was 6.3 percent in the streptokinase group and 7.1 percent in the placebo group. Of those treated within three hours of the onset of symptoms, 5.2 percent died in the streptokinase group (n = 477), as compared with 6.5 percent in the placebo group (n = 463). These differences were not significant. The time to peak serum levels of creatine kinase of myocardial origin (CK-MB) after the onset of symptoms was significantly shorter (13.9 vs. 19.2 hours), and the integrated area under the CK-MB curve (CK-MB infarct size) was significantly smaller, in the streptokinase group (P less than 0.02). Angiograms obtained in 848 patients three to four weeks after infarction revealed that the streptokinase group had higher global ejection fractions (56.8 vs. 53.9 percent, P less than 0.005) and regional ejection fractions (all patients in group, P less than 0.005; patients with anterior or inferior infarctions, P less than 0.05). We conclude that beginning intravenous streptokinase infusion early after the onset of myocardial infarction limits the size of the infarct regardless of its localization. There was, however, only a trend toward reduced mortality at 21 days.