Background: To further elucidate the mechanisms involved in the treatment of acute myocardial infarction (AMI) with angiotensin-converting enzyme inhibitors, we compared the effects on left ventricular volumes of early (< 48 hours) versus late (45 days) administration of a fixed low dose of enalapril (10 mg) in patients with AMI. We also analyzed the changes of left ventricular volumes after withdrawal of the study drug. Reduced dilation of the left ventricle is one of the beneficial effects of angiotensin-converting enzyme inhibition after AMI. However, the nature of this effect is not completely understood.
Methods and results: We included 89 patients within 48 hours after onset of a first AMI and radionuclide left ventricular ejection fraction less than 45%. The study was double-blind and compared enalapril and placebo with a crossover design. All patients were randomly assigned to a sequence A (enalapril, 45 days; placebo, 45 days) or B (placebo, 45 days; enalapril, 45 days). The end point was the change of left ventricular volume at 45 and 90 days. Thrombolysis was administered to 26 patients (70%) in group A and 25 (75%) in group B. All pretreatment clinical variables were similar in both groups. Median and 95% confidence intervals (CIs) of left ventricular diastolic volumes were 46.8 ml/m2 (39 to 61 ml/m2) and 46.6 ml/m2 (39 to 60 ml/m2) for groups A and B, respectively. Baseline end systolic volumes were 28.5 ml/m2 (20 to 36 ml/m2) and 28.9 ml/m2 (23 to 28 ml/m2) in the same groups. Placebo treatment during the initial 45 days was associated with an increase of left ventricular diastolic volume of 8.75 ml/m2 (95% CI, 3.25 to 17.1 ml/m2; p < 0.01) and end-systolic volume of 4.20 ml/m2 (95% CI, 0.00 to 10.1 ml/m2; p < 0.05). No significant changes during other phases of the study were observed. At 45 days left ventricular diastolic volume was 11.1 ml/m2 (95% CI, 0.5 to 2.2 ml/m2), greater in placebo-treated patients compared with patients receiving enalapril.
Conclusions: In patients with a first Q wave AMI and left ventricular ejection fraction less than 45%, treatment with enalapril can prevent left ventricular dilation. This protective effect involves at least partially a structural modification of the left ventricle. Hence, maximal benefit can be obtained only with early initiation of treatment.