A DOUBLE-BLIND RANDOMIZED MULTICENTER DOSE-RANGING TRIAL OF INTRAVENOUS STREPTOKINASE IN ACUTE MYOCARDIAL-INFARCTION

Intravenous streptokinase administration is now a widely applied therapy for patients in the early hours of acute myocardial infarction (AMI). The dosages used do not appear to be based on comparative clinical investigations. Therefore a doubleblind randomized trial was carried out to establish the optimal dose of streptokinase. A total of 189 patients who had symptoms of AMI for < 4 hours were treated with 200,000, 750,000, 1,500,000 or 3,000,000 IU streptokinase intravenously. At coronary angiography 2.8 ± 2.7 hours (mean ± standard deviation) after the start of streptokinase infusion, patency of the infarct-related coronary artery was observed in 38, 75, 60 and 82% of the patients, respectively, in the 4 groups. The result of the dosage of 200,000 IU was significantly poorer than that of the other dosages (p < 0.01). The result of a dosage of 3,000,000 IU was significantly better than that of 1,500,000 IU (p < 0.05), but the differences with 750,000 IU were not significant. Blood transfusion was required in 4 patients (2%), distributed over the 4 groups in 0, 2, 1 and 1 of the patients. One patient had major bleeding; this patient had been treated with 750,000 IU. The 3-month mortality-rate in the whole study population was 5%. Thus, of the 4 doses of streptokinase tested, 750,000 IU is the minimal therapeutic dosage, and the arguments for 1,500,000 IU as standard therapy for comparison with other fibrinolytic drugs are poor. The best results in this study were achieved with 3,000,000 IU, but further research will be needed to establish the efficacy and safety of this new regimen. © 1990.