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Intravenous Streptokinase in Acute Myocardial Infarction - ISAM
Description:
To assess the effect of streptokinase administered within 6 hours of symptom onset on early mortality in the setting of acute MI.
Hypothesis:
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
Exclusions:
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).
Interpretation:
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).
References:
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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