Copyright © 1987 by the European Society of Cardiology.
© 1987 The European Society of Cardiology
Randomized factorial trial of high-dose intravenous streptokinase, of oral aspirin and of intravenous heparin in acute myocardial infarction
ISIS (INTERNATIONAL STUDIES OF INFARCT SURVIVAL) PILOT STUDY INVESTIGATION**The names of the principal investigators are given immediately before the references
Received 26 September 1986; revised 23 March 1987; .
Address for Correspondence: Rory Collins, ISIS, Radchffe Infirmary, Oxford OX2 6HE, U.K.
Abstract
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. Using a '2 x 2 x 2 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 (1000 1U h-1 for 48 hours) or no heparin. Streptokinase (SK) was associated with a nonsignificant (NS) increase in non-fatal reinfarc–tion (3.9% SKvs 2.9% placebo) and decrease in mortality (7.5%vs9.7% in hospital plus 6.1%vs 8.7% after discharge). After SK, there were significantly fewer strokes (0.5% vs 2.4%; 2P<0.05), but significantly more minor adverse events (e.g. hypotension and bradycardial, allergies, bruises or minor bleeds, nausea). Aspirin was associated with fewer non-fatal reinfarctions (3.2% aspirin vs 39% placebo; NS), deaths (in hospital: 61% vs 10.5%; 2P<0.05, and after discharge: 7.0% vs 6.9%; NS), and strokes (0.3% vs 2.0%; NS). Heparin was associated with a decrease in reinfarction (2.2% heparin vs 4.9% no heparin; NS), though not in mortality (in hospital: 8.0% vs 8.5%; NS, and after discharge: 7.0% vs 6.9%; NS), and with a trend towards more strokes (1.6% vs 0.7%; NS) and more bruising and bleeding (14% vs 12%; NS). To assess more reliability the effects of aspirin and of this SK regimen on mortality, about 400 hospitals worldwide are now collaborating in a large (about 20 000 patients planned ) randomized trial ( ISIS-2). for which the present study was a pilot.
Key Words: Randomized controlled trial • fibrinolytic therapy • antiplatelet therapy • anticoagulant therapy • acute myocardial infarction
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