Enalapril to Prevent Cardiac Function Decline in Long-Term Survivors of Pediatric Cancer Exposed to Anthracyclines

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Abstract
Purpose: To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer. Patients and Methods: This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure. Results: There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m2; P = .55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (−8.59 v 1.85 g/cm2; P = .033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P = .11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P = .0003) and fatigue (10% v 0%; P = .013). Conclusion: Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.