Carvedilol for Children and Adolescents With Heart Failure

Abstract

temic ventricular dysfunction is a significant medical problem for children and represents the reason for at least 50% of pediatric referrals for heart transplantation. 1 To date, there have been no large randomized controlled trials of any medication in children and adolescents with chronic heart failure. Treatment recommendations in children and adolescents with heart failure are extrapolated from the results of clinical trials conducted in adults, which may be problematic. 2 Although multiple studies in adults have demonstrated beneficial effects of ␤-blockers on left ventricular function, symptoms, and survival, [3][4][5][6][7] little isFor editorial comment see p 1214.

Heart Failure in Children

“…No treatment effect of carvedilol on the primary composite end point of clinical heart failure outcomes was detected. 3 Shortening fraction improved significantly over time in all 3 study groups, and carvedilol therapy significantly improved shortening fraction compared to placebo. Ejection fraction improved significantly over time in all 3 groups as well, but there was no cross-group treatment effect, perhaps because of the strength of the within-group temporal trends.…”

“…Ejection fraction improved significantly over time in all 3 groups as well, but there was no cross-group treatment effect, perhaps because of the strength of the within-group temporal trends. 3 A prespecified analysis demonstrated a significant interaction effect between ventricular morphology and response to carvedilol, with a trend toward better clinical outcome in the subjects with DCM who received carvedilol and worse outcome in subjects with congenital heart disease who received carvedilol.…”

“…Age-adjusted modifications of heart failure scores can quantify the symptoms of heart failure in children and have been used both as inclusion criteria and as end points in several studies of heart failure in children. 2,3 Unfortunately, heart failure class at presentation is a poor predictor of worsening clinical outcome. 4,5 The scenario of a child with few symptoms who suddenly develops decompensated heart failure is well known and highlights the limitations of heart failure class as a predictor or outcome in children.…”

“…On the other hand, symptomatic improvement was reported in 55% of the subjects with improved ventricular ejection fraction. 3 This dichotomy of end points illustrates the need for further research to identify patients at risk for poor outcome and patients with the potential for full recovery. The mortality rate among children listed and waiting for heart transplantation has also declined but remains unacceptably high at 17%.…”

Recommendations to Enhance Pediatric Cardiovascular Drug Development: Report of a Multi‐Stakeholder Think Tank

“…Additionally, the composite endpoint that was used had not been validated in pediatric patients with heart failure. Finally, the study was underpowered because the rate of spontaneous improvement in placebo‐treated patients was underestimated, possibly stemming from a lack of prior natural history data in pediatric patients with heart failure 42. Investigating the pediatric‐specific dosing, natural history, and appropriate endpoints before performing a larger, randomized trial may lead to more efficient and meaningful pediatric trials in the future.…”