Carvedilol for children and adolescents with heart failure - A Randomized controlled trial
Carvedilol for children and adolescents with heart failure - A Randomized controlled trial
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DOI：
10.1001/jama.298.10.1171
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发表时间：
2007-09-12
影响因子：
120.7
通讯作者：
Tani, Lloyd Y.
中科院分区：
文献类型：
--
作者：
Shaddy, Robert E.;Boucek, Mark M.;Tani, Lloyd Y.
虽然-受体阻滞剂可以改善成人心力衰竭的症状和生存率，但对儿童和青少年的这些药物知之甚少。目的前瞻性评价卡维地洛治疗全身性室性收缩功能障碍的疗效。设计、环境和参与者：一项多中心、随机、双盲、安慰剂对照的研究，研究对象为来自美国26个中心的161名有症状性收缩期心力衰竭的儿童和青少年。除了常规的心力衰竭药物治疗外，患者还被分配接受安慰剂或卡维地洛。2000年6月开始入组，2005年5月最后一次给药（每位患者接受8个月的药物治疗）。干预措施患者按1:1:1的比例随机分配，每日两次服用安慰剂、低剂量卡维地洛（体重= 62.5 kg时每剂量0.2 mg/kg）或高剂量卡维地洛（体重= 62.5 kg时每剂量0.4 mg/kg），并根据每个患者的全身心室是否为左心室进行分层。主要结局指标主要结局指标是接受卡维地洛（低剂量和高剂量联合）与安慰剂的患者的心力衰竭结局的综合指标。次要疗效变量包括该组合的单个成分、超声心动图测量和血浆b型利钠肽水平。结果基于改善、恶化或不变患者百分比的复合终点，两组间无统计学差异。在54例安慰剂组患者中，30例改善（56%），16例恶化（30%），8例无变化（15%）；在103名使用卡维地洛的患者中，58名改善（56%），25名恶化（24%），20名无变化（19%）。病情恶化的比率低于预期。联合卡维地洛组与安慰剂组患者预后恶化的优势比为0.79 （95% CI, 0.36-1.59; P = 0.47）。预先指定的亚组分析注意到治疗与心室形态之间的显著相互作用（P = 0.02），表明在系统性左心室患者（有益趋势）和系统性左心室非左心室患者（非有益趋势）之间可能存在治疗效果的差异。结论这些初步结果表明卡维地洛不能显著改善有症状收缩期心力衰竭的儿童和青少年的临床心力衰竭结局。然而，考虑到低于预期的事件发生率，该试验可能力度不足。卡维地洛对儿童和青少年的心室形态可能有不同的影响。
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 high-dose carvedilol (0.4 mg/kg 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.