ISIS-2

Trial Details:

Acronym: International Study of Infarct Survival

Purpose: To evaluate the use of the thrombolytic drug streptokinase versus aspirin versus the combination of both for the treatment of acute myocardial infarction.

Format: Randomized, double blind, multicenter, two-by-two factorial placebo controlled trial

Treatment Group: Streptokinase OR the combination of streptokinase and aspirin

Control Group: Placebo

Number of Patients: 17,187

Inclusion Criteria:

• Suspected acute myocardial infarction within 24 hours of symptom onset
• No contraindication for streptokinase or aspirin

Exclusion Criteria:

• Prior stroke
• Prior GI bleed or peptic ulcer disease
• Recent trauma
• Severe refractory hypertension
• Recent arterial procedure
• Allergy to streptokinase or aspirin

Follow-up: Initially 5 weeks, but most recent publication followed for 10 years

Primary Endpoint: Cardiovascular mortality at 5 weeks

Secondary Endpoint:

• Non-fatal reinfarction or stroke
• Major bleeding requiring blood transfusion
• Intracranial hemorrhage

Summary:

Randomized acute MI patients to aspirin alone, streptokinase alone or both combined. The combination of the two was better than either agent alone. Aspirin reduced non-fatal reinfarction without increasing bleeding risk. Streptokinase alone increased bleeding requiring transfusion, intracranial hemorrhage and non-fatal re-infarction if used alone. Survival benefit of combination of aspirin and streptokinase extended out at least 10 years.

Original Publication:

Lancet. 1988 Aug 13;2(8607):349-60.

Bourke JP, et al. J Am Coll Cardiol. 1990 Dec;16(7):1703-10.

Baigent C, et al. BMJ. 1998 May 2;316(7141):1337-43.