Myocardial infarction: captopril decreases mortality.

Clinical bottom line (level 1b)

  1. Patients with acute myocardial infarction who are given captopril are less likely to die, tahn those given placebo (NNT = 24 at 2 years) .
  2. Patients who are given captopril are less likely to have treatment failure of congestive heart failure resulting in open label ACE inhibitor use (NNT = 18 at 2 years) .
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group : Lancet 1995; 345: 669-685
Expires March 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 45 centres, USA and Canada

2231 patients (aged mean 59 years, 83% male) Survived for at least three days after an acute myocardial infarction and left ventricular ejection fraction of 40% or less

Excluded if
  • aged <20 or >79
  • failure to undergo randomisation within 16 days after MI
  • relative contraindication to the use of angiotensin-converting-enzyme inhibitor or the need for such an agent to treat symptomatic congestive heart failure or systemic hypertension
  • serum creatinine level > 2.5 mg per decilitre (221 µ mol per litre)
  • other conditions believed to limit survival
  • unwillingness or inability to participate in a long-term trial
  • unstable course after infarction


    • Control Group: (n = 1116, 1116 analysed): placebo
    Experimental Group: (n = 1115, 1115 analysed): captopril - target dose was 25 mg three times daily by the end of the in-hospital phase; this dose was gradually increased to amaximum of 50 mg three times daily unless adverse effects were seen.

    100% followed for 2 years Range of follow-up was 24 to 60 months.
    Outcome notes:
    • failure of digitalis and diuretic agents to control congestive heart failure : requiring open-label angiotensin converting enzyme inhibitor therapy

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    mortality 2 years 275
    (24.6%)    		 228
    (20.5%)    		 17.0%
    (3.00% to 29.0%)    		 4.19%
    (0.73% to 7.66%)    		 24
    (13 to 137)
    failure of digitalis and diuretic agents to control congestive heart failure 2 years 179
    (16.0%)    		 118
    (10.6%)    		 34.0%
    (18.0% to 47.0%)    		 5.46%
    (2.65% to 8.27%)    		 18
    (12 to 38)

    Comments

    1. Compliance was calculated with the use of a pill count.

    Citation

    1. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group , : ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet 1995; 345: 669-685
    Contributor: Clare Wotton, January 2000
    Reviewer:

    Clinical Question.
    Patient acute myocardial infarction
    Intervention or Exposure captopril
    Comparison placebo
    Outcome mortality