Effects of the Beta-Adrenoceptor Blocker Carvedilol in Children with Myocardial Failure

Abstract

We performed a prospective, open study to evaluate the clinical effect of Carvedilol among pediatric patients with myocardial failure (CHF) failing to reply sufficiently to standard therapy. In addition, we assessed pharmacokinetic parameters of Carvedilol among these children. Pediatric patients were treated with oral Carvedilol in a ramped dosing scheme (initially 0.09mg/kg day followed by 0.18, 0.35 for two weeks each and 0.70mg/kg day as a target dose) in addition to ACE inhibitors, digoxin and diuretics. Clinical parameters (ejection fraction, modified Ross score) were assessed in a blinded manner before initiation of treatment and monthly up to six months. Pharmacokinetic profiles of Carvedilol were determined over the first 12-hour period following the initial dose and over another 12-hour period under steady state conditions following the target dose. Sixteen patients (between 6 weeks and 19 years of age) were enrolled in the study, including 10 patients with dilated cardiomyopathy and six with myocardial failure secondary to congenital heart diseases. All 16 patients tolerated the maximum target dose. After six months of Carvedilol therapy, ejection fraction was increased (37 ± 18% to 52 ± 21%; p < 0.05) and the modified Ross score was improved (5 ± 2 to 3 ± 3 points; p < 0.05). Elimination half-life (t_1/2) was 2.6 hours (range 1.49 to 3.66) in young (0.1 to 3.5 years of age, n = 7) and 5.3 hours (3.71 to 6.93; p < 0.05) in older pediatric patients (5.5 to 19 years of age, n = 7; p < 0.05). Overall, pediatric patients with CHF and failing standard therapy had a benefit from oral Carvedilol treatment. The increased elimination of Carvedilol in young children suggests that an increase in dosing might further improve the therapeutic response.