Ivabradine in Children With Dilated Cardiomyopathy and Symptomatic Chronic Heart Failure

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. T...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2017-09, Vol.70 (10), p.1262-1272
Main Authors: Bonnet, Damien, Berger, Felix, Jokinen, Eero, Kantor, Paul F., Daubeney, Piers E.F.
Format: Article
Language:English
Subjects:
Adolescent
Age
Benzazepines - administration & dosage
Beta blockers
Bradycardia
Brain natriuretic peptide
Cardiac arrhythmia
Cardiology
Cardiomyopathy
Cardiomyopathy, Dilated - diagnosis
Cardiomyopathy, Dilated - drug therapy
Cardiomyopathy, Dilated - physiopathology
Cardiovascular Agents - administration & dosage
Child
Child, Preschool
Children
Clinical trials
Dilated cardiomyopathy
Dosage
Dose-Response Relationship, Drug
Double-Blind Method
Echocardiography
Female
Follow-Up Studies
Heart diseases
Heart failure
Heart Failure - diagnosis
Heart Failure - drug therapy
Heart Failure - physiopathology
Heart rate
Humans
Infant
Ivabradine
left ventricular ejection fraction
Male
Medical diagnosis
N-terminal pro–B-type natriuretic peptide
Patients
pediatric
Pediatrics
Quality of Life
Stroke Volume - drug effects
Time Factors
Transplants & implants
Treatment Outcome
Ventricle
Ventricular Function, Left - drug effects
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Summary: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. 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. 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. 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. 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) [Display omitted]
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2017.07.725