Acute Infarction Ramipril Efficacy Study - AIRE

Description:

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

Hypothesis:

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.

Exclusions:

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
reinfarction
stroke
death.

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).

Interpretation:

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.

References:

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


< Back to Listings