Beta-blockers for children with congestive heart failure

Background

The term congestive heart failure describes a disorder in which the heart is unable to sufficiently and efficiently pump blood through the body. Depending on the severity of the condition, this causes breathlessness and fatigue due to insufficient oxygen supply, and an accumulation of fluids in tissues and organs.

In children, congestive heart failure is mainly due to congenital heart defects. Drug treatment, depending on the specific condition, may be used for long-term control of heart failure, or to bridge the time until corrective surgery. For dilated or restrictive cardiomyopathy, a disorder with high mortality, heart transplantation remains the only option when drug treatment fails.

Beta-blockers have proven beneficial and even life-saving in adults with congestive heart failure and therefore, are part of the standard treatment. For children, similar benefits could be expected, but beta-blockers are used, if at all, off-label (i.e. they are not recommended for children). Since the causes for heart failure are different in children than they are in adults, the main effect and adverse events may differ. Dosing might also have to be specifically adapted for different age groups.

Study characteristics

This review summarises and discusses the available information on the use of beta-blockers in children with congestive heart failure. Seven studies, with a total of 420 children were included in the review.

Key results

Beta-blocker therapy improved heart failure in four small studies with less than 30 participants each, and two larger studies with 80 participants each. However, the largest trial, with 161 participants, did not show a significant effect of the investigated beta-blocker over placebo.

None of the studies reported any severe beta-blocker-related adverse events, apart from one child who had a heart rhythm disturbance. 

Conclusions

There were not enough data to recommend or discourage the use of beta-blockers in children with congestive heart failure. However, the current available data suggest that children with heart failure might benefit from beta-blocker treatment. Further investigations are required to establish guidelines for therapy. 

Authors' conclusions: 

There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme. However, the sparse data available suggested that children with congestive heart failure might benefit from beta-blocker treatment. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are also required to provide effective dosing in future trials.

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Background: 

Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive heart failure in children differs from that in adults in terms of characteristics, aetiology, and drug clearance. Therefore, paediatric needs must be specifically investigated. This is an update of a Cochrane review previously published in 2009.

Objectives: 

To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS up to November 2015. Bibliographies of identified studies were checked. No language restrictions were applied.

Selection criteria: 

Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure.

Data collection and analysis: 

Two review authors independently extracted and assessed data from the included trials.

Main results: 

We identified four new studies for the review update; the review now includes seven studies with 420 participants. Four small studies with 20 to 30 children each, and two larger studies of 80 children each, showed an improvement of congestive heart failure with beta-blocker therapy. A larger study with 161 participants showed no evidence of benefit over placebo in a composite measure of heart failure outcomes. The included studies showed no significant difference in mortality or heart transplantation rates between the beta-blocker and control groups. No significant adverse events were reported with beta-blockers, apart from one episode of complete heart block. A meta-analysis of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) data showed a very small improvement with beta-blockers.

However, there were vast differences in the age, age range, and health of the participants (aetiology and severity of heart failure; heterogeneity of diagnoses and co-morbidities); there was a range of treatments across studies (choice of beta-blocker, dosing, duration of treatment); and a lack of standardised methods and outcome measures. Therefore, the primary outcomes could not be pooled in meta-analyses.