Safety of Enalapril in Infants: Data from the Pediatric Heart Network Infant with Single Ventricle Trial.

Objective To assess the safety profile of angiotensin converting enzyme (ACE) inhibitor therapy in infants with single ventricle (ISV). Study design The Pediatric Heart Network (PHN) conducted a double-blind trial involving infants with single ventricle physiology randomized to receive enalapril or placebo and followed to 14 months of age. Data including demographics, drug administration, hemodynamic monitoring, laboratory measurements, adverse events, and survival were extracted from the public use data set and compared between the placebo and enalapril-treated groups. Results The ISV trial randomized 230 patients, with 115 patients in each group. Initial enalapril dose was 0.10 mg/kg/day and median maximal dose was 0.38 mg/kg/day. There was no significant difference in change in blood pressure at study drug initiation or when resuming study drug after Glenn surgery. The incidence of hyperkalemia and neutropenia did not differ between groups. Renal dysfunction occurred in 3% of the enalapril group and none of the placebo patients, which was not statistically significant. There was a high frequency of serious adverse events in both groups. There was no difference in the frequency of heart transplant or death between groups. Conclusion Enalapril did not have sustained hemodynamic effects at initiation or up-titration of drug. Creatinine and potassium were not different between groups, although renal dysfunction occurred more often in the enalapril patients. Although efficacy of enalapril in neonates and single ventricles has not been demonstrated, the safety profile of ACE inhibitors appears to be low risk in infants and children with significant heart disease.