Acute Infarction Ramipril Efficacy Study - AIRE


Ramipril vs. placebo for mortality in heart failure after myocardial infarction.


Angiotensin converting enzyme inhibitor improves survival in the high risk subgroup of patients with acute myocardial infarction and evidence of heart failure.

Study Design

Study Design:

Patients Screened: 52,019
Patients Enrolled: 1,986
NYHA Class: 100% Class II or III
Mean Follow Up: 15 months (6 months)
Mean Patient Age: 65
Female: 26
Mean Ejection Fraction: not measured

Patient Populations:

Acute myocardial infarction (ECG and enzymes) and transient or persistent congestive heart failure after index infarct.

Clinical CHF by physical examination or radiography.


Severe (NYHA Class IV) CHF
Valvular or congenital heart disease
Unstable angina
Any contraindication to ACE inhibitor therapy.

Primary Endpoints:

Death (all cause mortality intention-to-treat).

Secondary Endpoints:

Time to first validated secondary event:
severe/resistant CHF

Drug/Procedures Used:

Ramipril (2.5 - 5 mg BID).

Concomitant Medications:

Aspirin (78%), Beta-blocker (22%), Calcium channel blockers (16%), Digoxin (12%), Diuretic (60%), Nitrate (56%)

Principal Findings:

All cause mortality significantly lower for Ramipril (17%) than placebo (23%).

Risk reduction with Ramipril was 27% (95% CI, 11% to 40%; p = 0.002).

Mortality reduction apparent as early as 30 days after initiation of treatment.

Risk reduction for first secondary endpoint was 19% (.95 CI 5-31%; p = 0.008).

Mortality benefit consistent across a range of subgroups with a trend toward less benefit in patients < 65 years and those not requiring a diuretic.

Ramipril reduced the risk of death from circulatory failure by 18%, but this did not reach statistical significance (95% CI; 41 to -14%; P = 0.237). The magnitude of the effects on sudden death and death due to circulatory failure were not significantly different. However, 38% of the reduction in overall mortality was from the subgroup with sudden death who had developed prior severe resistant heart failure (placebo n = 35, ramipril n = 15), again emphasizing the marked benefit in preventing failure.

At an average follow-up time of 15 months after randomization, all-cause mortality was lower in the ramipril group (16.9%) compared to placebo (22.6%), equivalent to an absolute mortality reduction of 5.7% and a relative risk reduction of 27% (95% CI 11-40%; p = 0.002). Three years after the AIRE study closed, mortality status of all patients was assessed through government records. Follow-up was for a minimum of 42 months and a mean of 59 months. Death from all causes had occurred in 83 (27.5%) of 302 patients randomly assigned ramipril and (38.9%) of 301 patients randomly assigned placebo. This 11.4% absolute mortality reduction was equal to a relative risk reduction of 36% (95% CI 15-52%; p = 0.002).


Ramipril reduces mortality and progression to resistant heart failure among patients with evidence of heart failure early after myocardial infarction. Retarding the progression of heart failure appears to be a major factor contributing to the reduction in mortality both by reducing circulatory failure and by reducing sudden death. Administration of ramipril to patients with post-MI CHF results in a large, sustained survival benefit.


1. Lancet 1993;342:821-828 Design and baseline results
2. Eur Heart J 1997; 18:41-51 Final results
3. Lancet 1997;349:1493-7 Extended follow-up (60 months)

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: Myocardial Infarction, Risk Reduction Behavior, Diuretics, Heart Failure, Electrocardiography, Ramipril, Death, Sudden, Cardiac

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