ISIS-4 trial

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ISIS-4 examined the role of the following interventions in the management of acute myocardial infarction:

  • one month of oral captopril
  • one month of oral isosorbide mononitrate
  • 24 hours of intravenous magnesium

Using captopril, there was a significant reduction in 5 week mortality versus placebo which appeared to be maintained in the long-term. There was an increase of:

  • 52 per 1000 in hypotension considered serious enough to require termination of study treatment
  • 5 per 1000 in reported cardiogenic shock
  • 5 per 1000 in some degree of renal failure

Using mononitrate, there was no significant reduction in 5 week mortality. There was an increase of 15 per 1000 in hypotension.

Using magnesium, there was no significant reduction in 5 week mortality.


  • in an acute MI, early treatment with an ACE inhibitor, in patients without clear contraindications, prevents about 5 deaths per 1000 in the first month
  • benefits appear to persist for at least the first year
  • benefits appear to be be greatest in high-risk patients


  • ISIS-4 (1995). ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected myocardial infarction. Lancet, 334,669-84.

Last reviewed 01/2018