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Carvedilol in Children With Heart Failure - Carvedilol in Children With Heart Failure
Description:
The goal of the trial was to evaluate treatment with carvedilol compared with placebo among children with heart failure.
Study Design
Study Design:
Patients Enrolled: 161
Mean Follow Up: 8 months
Mean Patient Age: Median age, 3 years
Female: 52
Mean Ejection Fraction: Baseline ejection fraction 26%
Patient Populations:
Age ≤17 years, chronic symptomatic heart failure due to systemic ventricular systolic dysfunction, New York Heart Association class II-IV for older children or Ross class II-IV for younger children for ≥1 month, and ejection fraction <40% in patients with systemic LV dysfunction or dilated ventricle with systemic ventricular systolic dysfunction in patients with no LV
Primary Endpoints:
Worsened, improved, or unchanged heart failure at 8 months
Drug/Procedures Used:
Patients were randomized in a double-blind manner to placebo (n = 55), low-dose carvedilol (target dose 0.4 mg/kg/d, max 25 mg), or high-dose carvedilol (0.8 mg/kg/d, max 50 mg) for 8 months. For the primary analysis, the carvedilol groups were pooled (n = 106).
Principal Findings:
At baseline, median ejection fraction was 26%, heart failure was class II in 71% and class III in 27%, and 74% of patients had systemic left ventricle (LV) dysfunction. Median BNP was 111 pg/ml. Patient age range was 3 months to 17 years.
The primary endpoint of change in heart failure at 8 months did not differ by treatment group, with improvements in 56% in both groups, unchanged in 15% of the placebo group and 19% of the carvedilol group, and worsening in 30% of the placebo group and 24% of the carvedilol group (p = 0.74). There was an interaction with ventricular morphology, with a nonsignificant benefit with carvedilol in the LV group (improvement 51% vs. 64%, odds ratio [OR] 0.28, 95% confidence interval [CI] 0.07-1.12) and a nonsignificant hazard with carvedilol in the non-LV group (improvement 67% vs. 35%, OR 1.71, 95% CI 0.78-3.76). There was no difference in mortality (OR 0.68, p = 0.55), or the composite of death or heart failure hospitalization (0.8, p = 0.52). Both treatment groups had improvements in ejection fraction from baseline to follow-up. There was no difference in withdrawals due to adverse events (13% in each group).
Interpretation:
Among children with heart failure, treatment with the beta-blocker carvedilol was not associated with changes in heart failure at 8 months compared with placebo.
The present trial is one of the first randomized studies of chronic heart failure conducted in children. Most therapies used in children for this condition are evaluated in trials of adults, and it is assumed the results will be applicable to children as well, although as this trial demonstrates, may not be the case. One unexpected finding in the trial was the high rate of improvement in heart failure in the placebo group, which was larger than expected. The presenters also noted the difficulty in enrolling children in randomized trials, as parents are often hesitant to expose children to unknown potential risks.
References:
Shaddy RE, Boucek MM, Hsu DT, et al. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA 2007;298:1171-9.
Presented by Dr. Robert Shaddy at the March 2006 ACC Annual Scientific Session, Atlanta, GA.
Keywords: Child, Carbazoles, Heart Failure, Propanolamines, Heart Ventricles, Hospitalization
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