Effect on exercise performance of enalapril therapy initiated early after myocardial infarction

Abstract

Objectives. The Nordic Enalapril Exercise Trial was a multicenter subtrial of the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II) designed to evaluate the effect on maximal exercise performance of a 6-month period of enalapril treatment initiated early after myocardial infarction.Background. When begun early after myocardial infarction, converting enzyme inhibition therapy has been shown to attenuate infarct expansion and reduce left ventricular volume. Therapy has been associated with improved exercise performance.Methods. Three hundred twenty-seven men (mean age 63.3 ± 10.9 years) with documented acute myocardial infarction were randomized to treatment with enalapril or placebo on a double-blind basis. Intravenous enalaprilat or placebo therapy was initiated within 24 h after the onset of symptoms. Oral therapy was continued at a target dose of 20 mg/day. Patients exercised maximally at 1 month and 6 months after infarction to symptom-limited end points on a cycle ergometer with a 20 W/min incremental protocol.Results. The treatment and control groups were comparable in patient age, concurrent therapy and type and site of infarction. At 1 month, for all patients, mean total work performed was 34.9 ± 20.9 kJ in the enalapril group (n = 169) versus 28.5 ± 20.6 kJ in the placebo group (n = 158) (difference = 18.4%, p < 0.01). This between-group difference in favor of enalapril was greatest in patients >70 years old (difference = 41.4%, p < 0.01, n = 105) and those with clinical evidence of heart failure (difference = 33.0%, p < 0.01, n = 122). At 6 months for all patients, mean total work performed was 35.4 ± 23.8 kJ in the enalapril group versus 34.0 ± 23.9 kJ in the placebo group (difference = 4.1%, NS).Conclusions. This trial found that chronic converting enzyme inhibition initiated early after myocardial infarction was associated with significantly greater exercise capacity in men tested at 1 month. This difference was independent of type or site of infarction, patient age or the presence of clinical heart failure. The difference between the treatment and control groups was not significant at 6 months because of improvement in the placebo group. Further research is needed to elucidate the potential mechanisms involved, profile those patients most likely to profit from early therapy and establish the optimal timing and duration for intervention.