ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS AFTER MYOCARDIAL-INFARCTION - INDICATIONS AND TIMING

A number of major studies have examined the impact of angiotensin conv erting enzyme inhibitors on mortality in patients with ischemic heart disease. However, in these studies, selection of patients, choice of a gent and timing of treatment after myocardial infarction have differed . In the Second Cooperative North Scandinavian Enalapril Survival Stud y (CONSENSUS II), all patients, unless hypotensive, were treated immed iately after thrombolysis with placebo or intravenous enalaprilat foll owed by oral therapy. In contrast, in the Survival and Ventricular Enl argement (SAVE) study, patients were selected with a reduced radionucl ide ejection fraction and without overt ongoing ischemia. Despite thes e different approaches, both studies were based on the rationale that angiotensin-converting enzyme inhibition would beneficially affect inf arct expansion and subsequent remodeling. The SAVE study reported a si gnificant reduction in mortality rate (19% risk reduction, 95% confide nce interval [CI] 3% to 32%) over an average follow-up period of 42 mo nths, but with no observable impact on mortality rate until almost 1 y ear into treatment. The CONSENSUS II trial closed prematurely, with no benefit (a 10% increase in risk, 95% CI 7% reduction to 29% increase) apparent from enalapril after 6 months of follow-up. The recently rep orted but unpublished findings of Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3) and the Fourth Interna tional Study of Infarct Survival (ISIS-4) indicate a small benefit fro m early (within 24 h) short-term (4 to 6 weeks) treatment of all patie nts, unless hypotensive, after a myocardial infarction. In contrast, t he Acute Infarction Ramipril Efficacy (AIRE) study demonstrated a mark ed reduction in mortality rate (27% risk reduction, 95% CI 11% to 40%) when the angiotensin-converting enzyme inhibitor ramipril was given t o patients manifesting some clinical evidence of heart failure, even i f transient, 3 to 10 days after myocardial infarction for an average p eriod of 15 months. Extrapolation from the findings of the AIRE study and from subgroup analyses of GISSI-3 and ISIS-4 indicate that patient s manifesting clinical evidence of heart failure after myocardial infa rction derive most of the benefit to be gained from the use of angiote nsin converting enzyme inhibitors. Appropriate selection of patients a nd careful timing of treatment after myocardial infarction to allow pa tients to achieve clinical stability will maximize potential benefit a gainst potential harm from these effective agents.