International Study of Infarct Survival-2 - ISIS-2


Streptokinase, aspirin, both, or neither for mortality in acute MI.


Whether the combination of SK and aspirin was better than either agent alone in preventing vascular death.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 17,187

Patient Populations:

Within 24 hours of the onset of symptoms of suspected MI.


History of stroke
Gastrointestinal hemorrhage or ulcer
Recent arterial puncture
Recent severe trauma
Severe persistent hypertension, allergy to SK or aspirin
Low risk of cardiac death
Other life-threatening disease

Primary Endpoints:

Death, vascular death, nonfatal reinfarction

Secondary Endpoints:

Bleeds requiring transfusion, stroke

Drug/Procedures Used:

SK, 1.5 x 106 U IV over 1 hour; aspirin, 162.5 mg qd orally.

Concomitant Medications:

Physicians allowed to use any other additional therapy considered appropriate

Principal Findings:

Reduction in 5-week vascular mortality with SK alone or aspirin alone

791 deaths (9.2%) with SK vs. 1029 (12.0%) with placebo (25% odds reduction; SD = 4; 2p <0.00001)

804 deaths (9.4%) with aspirin vs. 1016 (11.8%) with placebo (23% odds reduction; SD = 4; 2p <0.00001)

343 vascular deaths (8.0%) with SK plus aspirin vs. 568 (13.2%) with placebo (42% odds reduction; SD = 5; 95% confidence limit, 34-50%)

SK was associated with an excess of bleeds requiring transfusion (0.5% vs. 0.2% in the placebo group), but with fewer strokes (0.6% vs. 0.8%)

Aspirin significantly reduced nonfatal reinfarction (1.0% vs. 2.0% in the placebo group) and nonfatal stroke (0.3% vs. 0.6%)


The combination of streptokinase and aspirin was significantly better than either agent alone. Their separate effects on vascular death appeared to be additive.
The absolute mortality reductions appear to be greatest for patients at greatest risk of death (for example, women, older patients, hypotensive patients, patients with a previous MI or with anterior infarction).

SK may also be appropriate for patients with a below-average risk of cardiac death.

Worthwhile survival advantages can be obtained by routine use of antiplatelet therapy in almost all patients with suspected acute MI. The same can be said for the use of fibrinolytic therapy in a wide range of patients, including the elderly.


1. Lancet 1988;2:349-360. Final results
2. J Am Coll Cardiol 1988;(6 Suppl A):3A-13A. Final results

Keywords: Thrombolytic Therapy, Infarction, Stroke, Platelet Aggregation Inhibitors, Streptokinase

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