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A follow-up of the acute infarction ramipril Efficacy Study (AIRE) helps physicians determine how long patients who are given an ACE inhibitor should continue this therapy. AIRE was one of the major randomized trials with ACE inhibitors confirming that these drugs are life-saving in appropriately selected patients who have had a myocardial infarction (MI). The initial AIRE trial was published four years ago (Lancet 1993;342:821), and the trial was carried out in patients with acute MI who developed heart failure in hospital. Randomized patients were given ramipril or placebo for 12-13 months. The results indicated a substantial mortality benefit in the ACE inhibitor-treated patients. The current publication represents an extended follow-up of the original trial cohorts, with statistical analysis of risk reduction over an additional three years after cessation of randomized therapy. Physicians did not know what the patients had been taking, and use of an ACE inhibitor after termination of AIRE was at the discretion of the treating doctor. No data are available as to what medications these patients received.
The results indicate a continuing survival benefit in the ACE inhibitor cohort with total follow-up of five years. Hall and colleagues conclude that once a clinician has decided to treat a patient with an ACE inhibitor after an acute MI, therapy should be continued indefinitely, unless intolerance develops. They also stress the robust statistical power of the AIRE trial, comparable to SAVE and TRACE, but different from the much less clear benefits from the large GISSI-3 and ISIS-4 trials.
The results of this extension analysis of the AIRE cohorts are reassuring to those who believe that a selective approach to ACE inhibitor therapy post-MI is most appropriate. In MI patients with overt heart failure and/or severe depression of left ventricular function, ACE inhibitors have been conclusively shown to impart major survival benefits. There was a one-third risk reduction for death in AIRE in the ramipril-treated patients that persisted for five years, although active drug therapy in the trial itself lasted for only 12-13 months.
The AIRE patients had overt congestive heart failure based on clinical grounds, and those patients were treated with prolonged therapy, as opposed to European mega trials ISIS-4 and GISSI-3, which prescribed an ACE inhibitor for 5-6 weeks only and used a non-selective or all-comer’s approach. Hall et al recommend sustained treatment, and they also suggest that the drug dosage should be comparable to that employed in published clinical trials. I agree with this approach. The benefits from a non-selective approach to the use of ACE inhibitors are marginal at best, and for a variety of reasons, the ISIS-4 and GISSI-3 do not adequately support the recent recommendations from the GISSI-3 investigators that every patient receive an ACE inhibitor who has had an MI, irrespective of ejection fraction or clinical status.
This approach, while probably harmless, is reasonable as long as the physician reassesses the patient 1-3 months after the event to see whether continuation of ACE inhibitor therapy is necessary. It seems more logical to make an initial risk assessment based on ejection fraction and evidence of clinical heart failure, absence of reperfusion, or the presence of a large anterior infarction, and institute long-term ACE inhibitor therapy in these high-risk individuals. (Dr. Abrams is Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque.)