title: Carvedilol for children and adolescents with heart failure: a randomized controlled trial.
abstract: BACKGROUND
  Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents.
  
  
  OBJECTIVE
  To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction.
  
  
  METHODS
  A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months).
  
  
  METHODS
  Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not.
  
  
  METHODS
  The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels.
  
  
  RESULTS
  There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend).
  
  
  CONCLUSIONS
  These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00052026.
authors.affiliation: Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, USA. shaddyr@email.chop.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Shaddy
authors.forename: Mark M
authors.initials: MM
authors.lastname: Boucek
authors.forename: Daphne T
authors.initials: DT
authors.lastname: Hsu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boucek
authors.forename: Charles E
authors.initials: CE
authors.lastname: Canter
authors.forename: Lynn
authors.initials: L
authors.lastname: Mahony
authors.forename: Robert D
authors.initials: RD
authors.lastname: Ross
authors.forename: Elfriede
authors.initials: E
authors.lastname: Pahl
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Blume
authors.forename: Debra A
authors.initials: DA
authors.lastname: Dodd
authors.forename: David N
authors.initials: DN
authors.lastname: Rosenthal
authors.forename: Jeri
authors.initials: J
authors.lastname: Burr
authors.forename: Bernie
authors.initials: B
authors.lastname: LaSalle
authors.forename: Richard
authors.initials: R
authors.lastname: Holubkov
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Lukas
authors.forename: Lloyd Y
authors.initials: LY
authors.lastname: Tani
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000627:therapeutic use*; D002227:Carbazoles / Q000097:blood / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000077261:Carvedilol; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011412:Propanolamines / Q000097:blood / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013599:Systole; D018754:Ventricular Dysfunction / Q000150:complications*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain