Intravenous Streptokinase in Acute Myocardial Infarction - ISAM


To assess the effect of streptokinase administered within 6 hours of symptom onset on early mortality in the setting of acute MI.


Mortality by day 21 would be reduced in acute MI patients treated with streptokinase compared with placebo.

Study Design

Study Design:

Patients Enrolled: 1741
NYHA Class: not reported
Mean Follow Up: 21 days; long term follow-up 21 months
Mean Patient Age: not reported
Female: 18
Mean Ejection Fraction: EF at 3-4 weeks was significantly higher in the SK group than placebo group (56.9% vs 53.8%, p<0.005). Fewer patients treated with SK had an EF<=50% compared with placebo patients (30% vs 40%, p<0.005).

Patient Populations:

Age <=75 years Treatment within 6 hours of symptom onset ST elevations >=1 mm in the extremity leads of ECG and >=2 mm in the chest leads


Hemorrhagic diathesis; received oral anticoagulant treatment; received streptokinase within past 9 months; valvular heart disease and atrial fibrillation; peptic ulcer within past 6 months; colitis; esophageal varices; aortic aneurysm; history of severe therapy resistent hypertension; resuscitation wiht external cardiac massage; puncture of the subclavian or internal jugular vein; trauma; surgery within past 10 days; stroke; acute headache or visual disorders of unknown cause; implantation of a permanent pacemaker; any severe disease that would exclude the patient in the opinion of the clinical investigator.

Primary Endpoints:

Mortality at 21 days

Secondary Endpoints:

Cardiac mortality Nonfatal cardiac events Infarct size based on CKMB curves Ejection fraction 3-4 weeks after infarction Bleeding complications

Drug/Procedures Used:

Streptokinase (1.5 million U over 60 minutes) vs placebo

Concomitant Medications:

5000 IU heparin bolus; 800-1000 IU/h infusion for 72-96 hours (to maintain PTT 2-3 times control) 0.5 g aspirin 250 mg methylprednisolone

Principal Findings:

Mortality at 21 days was 6.3% in the streptokinase group and 7.1% in the placebo group (p=NS); likewise, there was no difference at 7 months (10.9% SK vs 11.1%) or 21 months (14.4% sk vs 16.1%). Mortality did not differ between the two groups when stratified by treatment within 3 hours of symptom onset (5.2% SK vs 6.5% placebo, p=NS) or 3-6 hours after onset (6.8% SK vs 7.7% placebo, p=NS). The reinfarction rate trended higher in the SK arm (2.3% vs 1.1%, p=0.06) as did unstable angina (5.7% vs 4.0%, p=0.09). Bleeding complications occurred more frequently in the SK group (5.9% vs 1.5%, p<0.0001). Time from treatment to peak CK-MB was shorter in the SK group (10.9 hr vs 16.1 hr, p<0.0001). Ejection fraction at 3-4 weeks was significantly higher in the SK group than the placebo group (56.9% vs 53.8%, p<0.005).


While the use of streptokinase within 6 hours of symptom onset reduced infarct size, there was no reduction in short- or long-term mortality. Mortality was lower than expected in the placebo group (7.1% vs 18% expected). Other larger studies such as GISSI-1 (n=11,802) did show a mortality reduction with SK (10.7% vs 13%, p=0.0002), suggesting the present study may have been underpowered to detect a mortality difference. Additional nonfatal complications occurred more frequently with SK (reinfarction, bleeding).


N Engl J Med 1986;314(23):1465-1471. Main results. J Am Coll Cardiol 1987;9(1):197-203. Long-term mortality and morbidity.

Keywords: Myocardial Infarction, Streptokinase, Electrocardiography

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