Carvedilol of no clear benefit for systolic heart failure in children

Abstract

Among children and adolescents with symptomatic systemic ventricular systolic dysfunction, does carvedilol improve heart failure symptoms compared with placebo? Multi-center, randomized, double-blind, placebo-controlled study. Enrollment began in June 2000, and the last dose was given in May 2005 (each patient received medication for 8 months). 26 centers in the United States. 161 children and adolescents (median age, 3 years) with symptomatic systolic heart failure. Etiologies of heart failure included dilated cardiomyopathy and congenital heart disease with both left and right systemic ventricular morphology. Patients were assigned to receive placebo or carvedilol in addition to treatment with conventional heart failure medications. The primary outcome was a composite measure of heart failure outcomes described as “worsened,” “improved,” or “unchanged.” This composite measure included heart failure class, need for hospitalization, requirement for discontinuation of study treatment, and global assessment score. There was no statistically significant difference in the groups for the composite end point on the basis of the percentage of patients whose outcome improved, worsened, or was unchanged. Of 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%). Of 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group versus the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A pre-specified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and patients whose systemic ventricle was not a left ventricle (non-beneficial trend). These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, because of the lower than expected event rates, the trial may have been under-powered. There may be a differential effect of carvedilol in children and adolescents on the basis of ventricular morphology.