Carvedilol for children and adolescents with heart failure - A Randomized controlled trial

被引:368
作者
Shaddy, Robert E.
Boucek, Mark M.
Hsu, Daphne T.
Boucek, Robert J.
Canter, Charles E.
Mahony, Lynn
Ross, Robert D.
Pahl, Elfriede
Blume, Elizabeth D.
Dodd, Debra A.
Rosenthal, David N.
Burr, Jeri
LaSalle, Bernie
Holubkov, Richard
Lukas, Mary Ann
Tani, Lloyd Y.
机构
[1] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA
[2] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA
[4] Columbia Univ, Coll Phys & Surg, New York, NY USA
[5] Univ S Florida, Dept Pediat, St Petersburg, FL 33701 USA
[6] Washington Univ, Dept Pediat, St Louis, MO 63130 USA
[7] Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA
[8] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA
[9] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA
[10] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[11] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA
[12] Stanford Univ, Med Ctr, Dept Pediat, Stanford, CA 94305 USA
[13] GlaxoSmithKline Inc, Philadelphia, PA USA
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2007年 / 298卷 / 10期
关键词
D O I
10.1001/jama.298.10.1171
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context 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. Design, Setting, and Participants 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). Interventions 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 >= 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 >= 62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. Main Outcome Measures 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.
引用
收藏
页码:1171 / 1179
页数:9
相关论文
共 33 条
[1]   Surrogate end points in heart failure [J].
Anand, IS ;
Florea, VG ;
Fisher, L .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2002, 39 (09) :1414-1421
[2]   Delisting of infants and children from the heart transplantation waiting list after carvedilol treatment [J].
Azeka, E ;
Ramires, JAF ;
Valler, C ;
Bocchi, EA .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2002, 40 (11) :2034-2038
[3]   Prospective single-arm protocol of carvedilol in children with ventricular dysfunction [J].
Blume, E. D. ;
Canter, C. E. ;
Spicer, R. ;
Gauvreau, K. ;
Colan, S. ;
Jenkins, K. J. .
PEDIATRIC CARDIOLOGY, 2006, 27 (03) :336-342
[4]   Registry of the International Society for Heart and Lung Transplantation: Eighth official pediatric report - 2005 [J].
Boucek, MM ;
Edwards, LB ;
Keck, BM ;
Trulock, EP ;
Taylor, DO ;
Hertz, MI .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2005, 24 (08) :968-982
[5]   Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure [J].
Bristow, MR ;
Gilbert, EM ;
Abraham, WT ;
Adams, KF ;
Fowler, MB ;
Hershberger, RE ;
Kubo, SH ;
Narahara, KA ;
Ingersoll, H ;
Krueger, S ;
Young, S ;
Shusterman, N .
CIRCULATION, 1996, 94 (11) :2807-2816
[6]   Mechanism of action of beta-blocking agents in heart failure [J].
Bristow, MR .
AMERICAN JOURNAL OF CARDIOLOGY, 1997, 80 (11A) :L26-L40
[7]   Carvedilol as therapy in pediatric heart failure: An initial multicenter experience [J].
Bruns, LA ;
Chrisant, MK ;
Lamour, JM ;
Shaddy, RE ;
Pahl, E ;
Blume, ED ;
Hallowell, S ;
Addonizio, LJ ;
Canter, CE .
JOURNAL OF PEDIATRICS, 2001, 138 (04) :505-511
[8]  
BURCH M, 1994, BRIT HEART J, V72, P246
[9]   CLINICAL PROFILE OF CONGESTIVE CARDIOMYOPATHY IN CHILDREN [J].
CHEN, SC ;
NOURI, S ;
BALFOUR, I ;
JUREIDINI, S ;
APPLETON, RS .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1990, 15 (01) :189-193
[10]   Decline in ventricular function and clinical condition after Mustard repair [J].
Derrick, G ;
Deanfield, JE .
EUROPEAN HEART JOURNAL, 2004, 25 (21) :1863-1864