619 patients with suspected acute myocardial infarction (MI) were randomized to receive either a high-dose short-term intravenous infusion of streptokinase (1.5 MU over one hour) or placebo. In addition, using a “2x2x2 factorial” design, patients were also randomized to receive either oral aspirin (325 mg on alternate days for 28 days) or placebo, and separately randomized to receive either intravenous heparin (1,000 IU/hour for 48 hours) or no heparin. Streptokinase (SK) was associated with a non-significant decrease in hospital mortality (7.7% allocated SI< vs 9.2% allocated placebo) and increase in non-fatal reinfarction (3.6% vs 2.9%). There were significantly more minor adverse events after SK (e.g. hypotension, allergies, bruises or minor bleeds), but no excess of strokes or of anaphylactic shock.Aspirin was associated with fewer reinfarctions (2.9% allocated aspirin vs 3.9% allocated placebo; NS), deaths (6.1% vs 10.5%; 2P<0.04) and strokes (0.3% vs 2.0%; 2P<0.1).Heparin was associated with a decrease in reinfarction (1.9% allocated heparin vs 4.9% allocated no heparin; 2P<0.04), though not in mortality (8.3% vs 8.2%; NS), and with a trend towards more strokes (1.6% vs 0.7%; NS) and more bruising and bleeding (14% vs 11%; NS). To assess reliably the effects of SK and aspirin on major endpoints, several hundred hospitals are now collaborating in a large (about 20,000 patients planned) randomized trial (ISIS-2).
ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither