Thorac Cardiovasc Surg 2018; 66(S 02): S111-S138
DOI: 10.1055/s-0038-1628322
Oral Presentations
Monday, February 19, 2018
DGPK: Basic Science and Clinical Studies
Georg Thieme Verlag KG Stuttgart · New York

Effect and Safety of Treatment with ACE-Inhibitor Enalapril and β-Blocker Metoprolol on the Onset of Left Ventricular Dysfunction in Duchenne Muscular Dystrophy: Results from a Six Years, Double-blind, Randomized Placebo-controlled Trial

S. Dittrich
1   Pediatric Cardiology, Erlangen University Hospital, Erlangen, Germany
,
E. Graf
2   Clinical Trials Unit of the Medical Center, University of Freiburg, Freiburg, Germany
,
U. Neudorf
3   Clinic for Pediatrics III, University Hospital Essen, Essen, Germany
,
A. Heilmann
4   Department of Pediatrics, University Hospital Carl Gustav Carus, Dresden, Germany
,
U. Schara
5   Pediatric Neurology, University Hospital Essen, Essen, Germany
,
J. Kirschner
6   Department of Neuropaediatrics and Muscle Disorders, University Medical Center, Freiburg, Germany
,
B. Stiller
7   Congenital Heart Defects and Pediatric Cardiology, Heart Center Freiburg University, Freiburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
22 January 2018 (online)

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Objectives: To assess the effect of a combined ACE-inhibitor and β-blocker therapy in 10- to 14-year-old boys with Duchenne muscular dystrophy and preserved left ventricular function.

Trial design Randomized double-blind placebo-controlled multicenter trial.

Methods: Boys with Duchenne muscular dystrophy were eligible for participation in 10 German centers. All patients were allocated on a combined enalapril and metoprolol therapy for 16 weeks and after that randomly assigned in a one-to-one ratio to continue medication or to a wash-out protocol for placebo treatment for 3–6 years. Objective of the study was to verify expected delay on the onset of left ventricular dysfunction in the treatment group. Primary outcome measure was LV-FS < 28% by biannually echocardiography. Secondary endpoints comprised chances of LV-SF from baseline, safety and side effects of medication, quality of life as assessed by KINDL-questionnaire, heart rate and autonomic function in ECG and Holter-ECG, cardiac biomarker and neurohumeral serum parameters, transthoracic echocardiography and tissue-Doppler analyses.

Results: Patient recruitment took place from March 2010 to December 2013 and last patient visit took place in December 2015. 42 boys gave informed consent, 41 started open run-in medication. 38 patients were randomized after run-in period: 21 to continue active medication, 17 patients to receive placebo. All patients could be included into analysis. Primary endpoint was reached in 6/21 versus 7/17 patients. Cox regression adjusted for left ventricular shortening fraction after run-in showed a statistically non-significant benefit for medication over placebo (hazard ratio [HR]: 0.38; 95% confidence interval [CI]: 0.12–1.22; p = 0.10). Adverse events did not differ between medication and placebo.

Conclusion: Initiation of therapy with ACE-inhibitor enalapril and β-blocker metoprolol when cardiac damage is minimal in younger Duchenne patients after 10 years of age delays deterioration of cardiomyopathy. Long-term therapy is safe and well tolerated without impact on quality of life.

Funding: This study (EudraCT-number 2009–009871–36) was paid by a grant from the Bundesministerium für Bildung und Forschung (BmBF) Förderkennzeichen 01KG0912. Implementation of the study was supported by the Competence Network for Congenital Heart Defects, which has received funding from the BmBF, grant number 01GI0601 (until 2014), and the DZHK as of 2015