More than 134,000 patients from over 20 countries took part in four large simple trials between 1981 and 1993, coordinated from Oxford, England.
[1][2] The First International Study of Infarct Survival (ISIS-1) was a placebo-controlled trial of the beta-blocker atenolol.
[3] The Second International Study of Infarct Survival (ISIS-2) was a 2×2 factorial placebo-controlled trial of aspirin and the thrombolytic drug streptokinase.
[4] The Third International Study of Infarct Survival (ISIS-3) was a 3×2 factorial trial that compared the three thrombolytic drugs streptokinase, tissue plasminogen activator (tPA) and anistreplase to each other, and also compared the anticoagulant heparin to no heparin.
[5] The Fourth International Study of Infarct Survival (ISIS-4) was a 2×2×2 factorial placebo-controlled trial of the angiotensin-converting enzyme inhibitor (ACE inhibitor) captopril, isosorbide mononitrate and magnesium sulphate.