@article{Bonnet:2017:10.1016/j.jacc.2017.07.725,
author = {Bonnet, D and Berger, F and Jokinen, E and Kantor, PF and Daubeney, PEF},
doi = {10.1016/j.jacc.2017.07.725},
journal = {Journal of the American College of Cardiology},
pages = {1262--1272},
title = {Ivabradine in Children With Dilated Cardiomyopathy and Symptomatic Chronic Heart Failure},
url = {http://dx.doi.org/10.1016/j.jacc.2017.07.725},
volume = {70},
year = {2017}
}

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TY  - JOUR
AB  - BackgroundHeart 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.ObjectivesThe 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.MethodsThis 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.ResultsThe 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.ConclusionsIvabradine safely reduced the resting heart rate of children with chronic HF and dilated cardiomyopathy. Ivabradine’s effect on heart rate was variable, highlighting the
AU  - Bonnet,D
AU  - Berger,F
AU  - Jokinen,E
AU  - Kantor,PF
AU  - Daubeney,PEF
DO  - 10.1016/j.jacc.2017.07.725
EP  - 1272
PY  - 2017///
SN  - 0735-1097
SP  - 1262
TI  - Ivabradine in Children With Dilated Cardiomyopathy and Symptomatic Chronic Heart Failure
T2  - Journal of the American College of Cardiology
UR  - http://dx.doi.org/10.1016/j.jacc.2017.07.725
VL  - 70
ER  - 

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