ISIS-3 trial

41299 patients entering hospital up to 24 hr after the onset of symptoms of acute myocardial infarction were randomised to:

• thrombolysis:
  • streptokinase (1.5 MU infused over 1 hr)
  • t-PA (0.60 MU/kg infused over 4 hr)
  • APSAC (30 U over 30 min)
    
    
• anticoagulation:
  • aspirin alone (162 mg/day)
  • aspirin plus subcutaneous heparin (12500 IU starting at 4 hr, given twice daily for 7 days)

The study showed that there was no significant difference in the mortality and complication rates between the three thrombolytic groups.

There was a small, but significant, deficit in re-infarctions in the t-PA group. Streptokinase had a small but significant deficit in non-cerebral bleeds. APSAC and streptokinase were associated with a higher frequency of allergic and hypotensive episodes.

ISIS-3 suggests that the use of heparin and aspirin rather than aspirin alone resulted in a slightly lower mortality rate in the short-term (although there was no effect at 6 months).

Reference:

• ISIS-3: a randomised comparison of streptokinase vs. tissue plasminogen activator vs. anistreplase and of aspirin plus heparin vs. aspirin alone among 41299 cases of suspected acute myocardial infarction. (1992). Lancet, 339, 753-770.