Ivabradine in Children With Dilated Cardiomyopathy and Symptomatic Chronic Heart Failure
Ivabradine in Children With Dilated Cardiomyopathy and Symptomatic Chronic Heart Failure
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DOI：
10.1016/j.jacc.2017.07.725
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发表时间：
2017-09-05
影响因子：
24
通讯作者：
Daubeney, Piers E. F.
中科院分区：
文献类型：
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作者：
Bonnet, Damien;Berger, Felix;Daubeney, Piers E. F.
背景心率降低作为治疗目标已在心力衰竭（HF）成人中进行了研究。伊伐布雷定已显示出有希望的疗效，但尚未在儿童中进行评价。目前，慢性儿童HF的治疗建议主要基于成人慢性HF指南。结论作者探讨了伊伐布雷定在扩张型心肌病和症状性慢性HF儿童中的剂量-反应关系。主要终点是心率较基线降低>= 20%，但不诱导心动过缓或症状。方法这是一项随机、双盲、安慰剂对照、II/III期研究，随访12个月。接受稳定HF治疗的儿童（n = 116）随机接受伊伐布雷定或安慰剂治疗。初始滴定期后，调整剂量以达到主要终点。左室功能（超声心动图），临床状态结果：73名服用伊伐布雷定的儿童中有51名（70%）达到了主要终点，而41名服用不同剂量安慰剂的儿童中有5名（12%）达到了主要终点（比值比：17.24; p < 0.0001）。基线至12个月期间，伊伐布雷定组患者的左心室射血分数增幅大于安慰剂组（13.5% vs. 6.9%; p = 0.024）。12个月时伊伐布雷定组纽约心脏协会功能分级或Ross分级的改善程度高于安慰剂组（38% vs. 25%; p = 0.24）。伊伐布雷定与安慰剂相比，QOL有改善趋势（p = 0.053）。两组的N末端B型利钠肽前体水平下降相似。伊伐布雷定和安慰剂的不良事件报告频率相似。结论伊伐布雷定可安全降低慢性心力衰竭和扩张型心肌病患儿的静息心率。伊伐布雷定对心率的影响是可变的，突出了剂量滴定的重要性。伊伐布雷定治疗改善了左心室射血分数，临床状态和QOL显示出有利趋势。（在6个月至18岁的扩张型心肌病和症状性慢性心力衰竭儿科患者中确定伊伐布雷定的有效和安全剂量; ISRCTN 60567801）（C）2017，美国心脏病学会基金会。
BACKGROUND Heart rate reduction as a therapeutic target has been investigated in adults with heart failure (HF). Ivabradine has shown promising efficacy, but has not been evaluated in children. Currently, treatment recommendations for chronic pediatric HF are based mainly on chronic HF guidelines for adults.OBJECTIVES The authors explored the dose-response relationship of ivabradine in children with dilated cardiomyopathy and symptomatic chronic HF. The primary endpoint was >= 20% reduction in heart rate from baseline without inducing bradycardia or symptoms.METHODS This was a randomized, double-blind, placebo-controlled, phase II/III study with 12 months of follow-up. Children (n = 116) receiving stable HF therapy were randomized to either ivabradine or placebo. After an initial titration period, the dose was adjusted to attain the primary endpoint. Left ventricular function (echocardiography), clinical status (New York Heart Association functional class or Ross class), N-terminal pro-B-type natriuretic peptide, and quality of life (QOL) were assessed.RESULTS The primary endpoint was reached by 51 of 73 children taking ivabradine (70%) versus 5 of 41 taking placebo (12%) at varying doses (odds ratio: 17.24; p < 0.0001). Between baseline and 12 months, there was a greater increase in left ventricular ejection fraction in patients taking ivabradine than placebo (13.5% vs. 6.9%; p = 0.024). New York Heart Association functional class or Ross class improved more with ivabradine at 12 months than placebo (38% vs. 25%; p = 0.24). There was a trend toward improvement in QOL for ivabradine versus placebo (p = 0.053). N-terminal pro-B-type natriuretic peptide levels decreased similarly in both groups. Adverse events were reported at similar frequencies for ivabradine and placebo.CONCLUSIONS Ivabradine safely reduced the resting heart rate of children with chronic HF and dilated cardiomyopathy. Ivabradine's effect on heart rate was variable, highlighting the importance of dose titration. Ivabradine treatment improved left ventricular ejection fraction, and clinical status and QOL showed favorable trends. (Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure from ages 6 months to 18 years; ISRCTN60567801) (C) 2017 by the American College of Cardiology Foundation.