Myocardial infarction: ramipril decreased death.

Clinical bottom line (level 1b)

  1. Patients with acute myocardial infarction who were given ramipril were less likely to die than those given placebo (NNT = 16 at 6 months) .
  2. Patients given ramipril were less likely to suffer severe/resistant heart failure than those given placebo (NNT = 19 at 6 months) .
  3. There was no clear difference in reinfarction or stroke.
The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators : Lancet 1993; 342: 821-828
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 144 centres, Argentina, Austria, Belgium, Denmark, Finland, Germany, Ireland, Italy, Luxembourg, Netherlands, South Africa, Sweden, Switzerland and the UK

2006 patients (aged mean 65 years, 73% male) Acute myocardial infarction and clinical evidence of heart failure admitted to coronary care, intensive care or general medicine units. Acute myocardial infarction was diagnosed as evolving ECG diagnostic of MI and abnormal cardiac enzymes. Clinical heart failure was defined as at least one of: evidence of left ventricular failure, evidence of pulmonary oedema, auscultatory evidence of a third heart sound with persistent tachycardia

Excluded if
  • renal failure
  • sustained hypotension
  • <18 years
  • severe heart failure (New York Heart Association grade IV)
  • heart failure of primary valvular or congenital aetiology
  • unstable angina
  • any recognised contraindication to angiotensin converting enzyme inhibitors
  • no consent or follow-up impracticable


    • Note:
  • 20 patients from a single centre were excluded because of concerns regarding data validity.


    • Control Group: (n = 982, 982 analysed): placebo 2.5 mg twice daily, increased to 5 mg
    Experimental Group: (n = 1004, 1004 analysed): 2.5 mg ramipril twice daily between day 3 and day 10 after AMI. If tolerated for 2 days, the dose was increased to 5 mg twice daily.
    The dose of drug remained the same in patients who could not tolerate 5 mg, and decreased to 1.25 mg in patients who could not tolerate 2.5 mg.
    99.9% followed for 6 months with mean follow-up of 15 months
    Outcome notes:
    • death, reinfarction, stroke or heart failure : (combined secondary end-point)

    The evidence

    Endpoints based on Kaplan-Meier analysis
    Outcome Time to outcome CER RR
    (95% CI)    		 NNT
    (95% CI)
    all-cause mortality 6 months 222/982
    (23%)    		 0.73
    (0.60 to 0.89)     		16
    (11 to 40)
    death, reinfarction, stroke or heart failure 6 months 337/982
    (34%)    		 0.81
    (0.69 to 0.95)     		15
    (9 to 49)

    Endpoints based on raw data and average follow-up
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    severe/resistant heart failure 6 months 178
    (18.1%)    		 143
    (14.2%)    		 21.0%
    (4.00% to 36.0%)    		 3.88%
    (0.65% to 7.12%)    		 26
    (14 to 155)
    reinfarction 6 months 88
    (8.96%)    		 81
    (8.07%)    		 10.0%
    (-20.0% to 33.0%)    		 0.89%
    (-1.56% to 3.35%)    		 112
    (NNT = 30 to infinity;
    NNH = 64 to infinity)
    stroke 6 months 17
    (1.73%)    		 25
    (2.49%)    		 -44.0%
    (-165% to 22.0%)    		 -0.76%
    (-2.02% to 0.50%)    		 -132
    (NNT = 198 to infinity;
    NNH = 49 to infinity)

    Comments

    1. The delayed administration of ramipril in this study probably accurately represents current practice patterns.

    Citation

    1. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators , : Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993; 342: 821-828
    Contributor: Clare Wotton and Bob Phillips, December 1999
    Reviewer: Arnold Baas

    Clinical Question.
    Patient acute myocardial infarction
    Intervention or Exposure ramipril
    Comparison placebo
    Outcome mortality and morbidity