EBM Consult

ISIS-2: Second International Study of Infarct Survival

ISIS-2 was a landmark trial that resulted in the integration of aspirin in the acute management of acute myocardial infarction (AMI) and established the fact that taking at least 162 mg of aspirin during or up to 24 hours after the onset of symptoms and continuing it daily will reduce their risk for 35-day vascular related mortality by 23%, as well as risks for reinfarction, stroke, and death from CVD.

  • When ASA was combined with streptokinase the reduction in mortality was increased to 42%
  • MIs were STEMI (54%), ST segment depression (8%), and other ECG abnormalities (27%)

ISIS-2: Second International Study of Infarct Survival

  • Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2:349-360. PubMed
    Study Design International, Multicenter, Prospective, Randomized (2x2 Factorial Design), Placebo-Controlled Trial
    Sample Size n = 17,187 (from 1985 - 1987)
      • Streptokinase 1.5 MU IV x 1 hr (n = 8592) vs. Placebo (n = 8595)
      • Aspirin 162 mg orally (n = 8587) vs Placebo (n = 8600)
      • Streptokinase 1.5 MI UV x 1 hr + aspirin 162 mg (n = 4292) vs Placebo (n= 4300)
      Other Treatments Anticoagulants and beta-blockers
      Follow Up Up to 34 months
      Primary Endpoint Vascular mortality at in the first 5 weeks of use
        • Streptokinase alone produced a highly significant reduction in 5-week vascular mortality: 791/8592 (9.2%) vs 1029/8595 (12.0%) with placebo (odds reduction: 25%; 2p < 0.00001)
          • Aspirin alone resulted in 804/8587 (9.4%) vascular deaths vs 1016/8600 (11.8%) with placebo (odds reduction: 23% 4; 2p <0.00001).
          • The combination of streptokinase and aspirin was significantly (2p less than 0.0001) better than either agent alone.
          • Streptokinase was associated with an excess of bleeds requiring transfusion (0.5% vs 0.2%) and of confirmed cerebral haemorrhage (0.1% vs 0.0%), but with fewer other strokes (0.6% vs 0.8%). These "other" strokes may have included a few undiagnosed cerebral haemorrhages, but still there was no increase in total strokes (0.7% streptokinase vs 0.8% placebo infusion).
          • Aspirin significantly reduced non-fatal reinfarction (1.0% vs 2.0%) and non-fatal stroke (0.3% vs 0.6%), and was not associated with any significant increase in cerebral haemorrhage or in bleeds requiring transfusion.
          • An excess of non-fatal reinfarction was reported when streptokinase was used alone, but this appeared to be entirely avoided by the addition of aspirin. Those allocated the combination of streptokinase and aspirin had significantly fewer reinfarctions (1.8% vs 2.9%), strokes (0.6% vs 1.1%), and deaths (8.0% vs 13.2%) than those allocated neither.
          • The differences in vascular and in all-cause mortality produced by streptokinase and by aspirin remain highly significant (2p < 0.001 for each) after the median of 15 months of follow-up.
          Conclusions Streptokinase alone and aspirin alone each produced a highly significant reduction in 5-week vascular mortality.
          Location Throughout Europe and United States
          Funding Behringwerke (a subsidiary to Hoechst the maker of Streptase)
          Comments 54% of patients had STEMI, 8% had ST segment depression, 27% had some other ECG abnormality.

        MESH Terms & Keywords

        • ISIS-2 Clinical Trial, Second International Study of Infarct Survival, Aspirin Use for Secondary Prevention of MI, Streptokinase for MI