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
Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, USA.
JAMA. 2007 Sep 12;298(10):1171-9. doi: 10.1001/jama.298.10.1171.
Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents.
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).
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.
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.
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).
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.
clinicaltrials.gov Identifier: NCT00052026.
尽管β受体阻滞剂可改善成年心力衰竭患者的症状并提高生存率，但对于儿童和青少年使用这些药物的了解甚少。
前瞻性评估卡维地洛对有症状的系统性心室收缩功能障碍的儿童和青少年的影响。
设计、地点和参与者：一项多中心、随机、双盲、安慰剂对照研究，研究对象为来自美国26个中心的161名有症状收缩性心力衰竭的儿童和青少年。除了使用传统的心力衰竭药物治疗外，患者被分配接受安慰剂或卡维地洛。2000年6月开始入组，2005年5月给予最后一剂（每位患者接受药物治疗8个月）。
患者按1:1:1的比例随机分为每日两次服用安慰剂、低剂量卡维地洛（体重<62.5 kg时每剂0.2 mg/kg，体重≥62.5 kg时每剂12.5 mg）或高剂量卡维地洛（体重<62.5 kg时每剂0.4 mg/kg，体重≥62.5 kg时每剂25 mg），并根据每位患者的系统性心室是否为左心室进行分层。
主要结局是接受卡维地洛（低剂量和高剂量合并）与安慰剂治疗的患者心力衰竭结局的综合指标。次要疗效变量包括该综合指标的各个组成部分、超声心动图测量指标和血浆B型利钠肽水平。
基于病情改善、恶化或未改变的患者百分比，各治疗组间的综合终点无统计学显著差异。在分配接受安慰剂治疗的54例患者中，30例病情改善（56%），16例病情恶化（30%），8例未改变（15%）；在分配接受卡维地洛治疗的103例患者中，58例病情改善（56%），25例病情恶化（24%），20例未改变（19%）。病情恶化率低于预期。卡维地洛联合治疗组与安慰剂组患者病情恶化结局的比值比为0.79（95%CI，0.36 - 1.59；P = 0.47）。一项预先设定的亚组分析指出治疗与心室形态之间存在显著交互作用（P = 0.02），表明在系统性左心室患者（有益趋势）和系统性心室不是左心室的患者（无益趋势）之间，治疗可能存在差异效应。
这些初步结果表明，卡维地洛对有症状收缩性心力衰竭的儿童和青少年的临床心力衰竭结局没有显著改善作用。然而，鉴于事件发生率低于预期，该试验可能效力不足。基于心室形态，卡维地洛在儿童和青少年中可能存在差异效应。
clinicaltrials.gov标识符：NCT00052026。
