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Do all roads lead to Rome?

by Peter F. Cohn, MD

Peter F. Cohn, MD,
is chief of cardiology emeritus, Department of Medicine, State University of New York Health Sciences Center, Stony Brook.

The problem of managing acute myocardial infarction (MI) in elderly patients, especially in those patients with left ventricular dysfunction, has multiple components, not the least of which is to decide which class of agents to use first (angiotensin-converting enzyme [ACE] inhibitors, diuretics, β blockers, etc) and whether to use these agents alone or in combination with 1 or more of the other classes of drugs. But the type of agent to be used can be a further subject for discussion depending on whether or not there is a “class effect.” For example, do all ACE inhibitors have the same benefits and drawbacks, or is one superior to the others?

This latter question is the one Dr Louise Pilote has asked. She performed a retrospective cohort study linking hospital discharge and prescription databases that provided information on 18453 Canadian patients over the age of 65 who were hospitalized for an acute MI in 109 hospitals between 1996 and 2000. In this large group, 7512 patients were started on ACE inhibitors within 30 days of discharge and continued using the same ACE inhibitor for at least 1 year. The ACE inhibitors included enalapril (Vasotec), fosinopril (Monopril), captopril (Capoten), quinapril (Accupril), lisinopril (Prinivil, Zestril), perindopril (Aceon), and ramipril (Altace). Survival benefits were best with ramipril. In an extensive discussion, the author explains the reasons she thinks all ACE inhibitors are not equal in the reduction of post-infarction mortality. Most important to her are the structural differences in the chemical compounds of the various drugs. But as Dr Pilote readily admits, the mechanisms for the differing effects remain unclear despite the various theories proposed. Even given the caveats of this study, it is still thought provoking.

One could conclude that when it comes to the benefits of ACE inhibitors in post-MI patients over the age of 65, not all roads lead to Rome; that is, not all ACE inhibitors lead to equivalent post-infarction survival. This may well be the first study to evaluate the long-term effects of several ACE inhibitors in a multiple head-to-head protocol. The limitations of an observational study relying on an administrative database are outlined by Dr Pilote and include hidden biases that are difficult to adjust for. Nevertheless, at a minimum, the positive results of prior post-MI ramipril studies1,2 seem to be confirmed by this study, although discarding other ACE inhibitors appears to be premature.

References
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(8875): 821-828.

2. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, rami­pril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342 (10):145-153.


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