Randomised Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither Among 17,187 Cases of Suspected Acute Myocardial Infarction (ISIS-2)

ISIS-2 is one of the most important trials in the history of cardiology — the study that put aspirin at the center of heart-attack treatment, where it remains.

In more than 17,000 patients with suspected acute myocardial infarction, the trial tested clot-dissolving streptokinase, oral aspirin, both, or neither. Each treatment independently cut 5-week vascular mortality, and the combination was additive, producing a 42 percent reduction in vascular death. Aspirin alone — a cheap, ubiquitous pill — also reduced reinfarction and stroke. The simplicity and magnitude of the aspirin benefit were revelatory.

The trial established two pillars of acute MI care simultaneously, and aspirin’s role in it transformed a humble drug into a life-saving standard. Its rigorous 2×2 factorial design also became a model for trial methodology.

We rate the evidence very strong, with very high clinical significance. A large, landmark randomized trial, ISIS-2 reshaped the treatment of heart attacks and remains foundational.