In adults, treatment of congestive heart failure with beta-blockers is well established. However, few data support beta-blocker use in children. Physicians cannot extrapolate adult findings to pediatric populations. This is because of developmental changes in myocardium, and differences in drug metabolism and elimination.

An ongoing open study provides new data regarding the pharmacology and clinical effect of carvedilol in children. Dr. Laer described this study, which includes pediatric patients who were clinically stable without further improvement of ventricular function. Ten had dilated cardiomyopathy, and six had congestive heart failure secondary to congenital heart disease.

All children received standard therapy including angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Investigators started oral carvedilol with a test dose of .09 mg/kg and increased to a target dose of .35 mg/kg twice daily. Treatment with the beta-blocker lasted at least six months.

Ventricular function has improved for the 12 patients (aged 6 months to 19 years) who have completed the study. Mean ejection fraction increased significantly, from 37% to 52%. As clinical symptoms improved, mean scores on a scale for severity of pediatric heart failure decreased significantly, from approximately 5 to 3 points.

Pharmacokinetic analysis revealed an age-dependent increase in elimination half-life of carvedilol. In addition, carvedilol concentration at half maximal heart rate reduction was lower in the younger patients.

Because of these findings, Dr. Laer and colleagues now accelerate the titration schedule from 4 to 2 weeks in younger patients. They may try increasing the target dose in the future. This may possibly provide more clinical benefit.

While these results are promising, the study is small and uncontrolled. Dr. Laer said investigators should assess the benefit in larger, randomized controlled trials. Such a study is underway right now in the United States.