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Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial

BACKGROUND: Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objecti...

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Autores principales: Raman, Subha V., Hor, Kan N., Mazur, Wojciech, He, Xin, Kissel, John T., Smart, Suzanne, McCarthy, Beth, Roble, Sharon L., Cripe, Linda H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319045/
https://www.ncbi.nlm.nih.gov/pubmed/28219442
http://dx.doi.org/10.1186/s13023-017-0590-8
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author Raman, Subha V.
Hor, Kan N.
Mazur, Wojciech
He, Xin
Kissel, John T.
Smart, Suzanne
McCarthy, Beth
Roble, Sharon L.
Cripe, Linda H.
author_facet Raman, Subha V.
Hor, Kan N.
Mazur, Wojciech
He, Xin
Kissel, John T.
Smart, Suzanne
McCarthy, Beth
Roble, Sharon L.
Cripe, Linda H.
author_sort Raman, Subha V.
collection PubMed
description BACKGROUND: Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. RESULTS: Eleven subjects (phase 1 baseline median [range] age: 13 [7 – 25] years) from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045). During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE) with preserved ejection fraction (EF). The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV) systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9%) in younger subjects whereas older subjects’ strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%). EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. CONCLUSIONS: Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. TRIAL REGISTRATION: http://ClinicalTrials.gov identifier NCT01521546. Registered 26 January 2012.
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spelling pubmed-53190452017-02-24 Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial Raman, Subha V. Hor, Kan N. Mazur, Wojciech He, Xin Kissel, John T. Smart, Suzanne McCarthy, Beth Roble, Sharon L. Cripe, Linda H. Orphanet J Rare Dis Research BACKGROUND: Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. RESULTS: Eleven subjects (phase 1 baseline median [range] age: 13 [7 – 25] years) from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045). During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE) with preserved ejection fraction (EF). The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV) systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9%) in younger subjects whereas older subjects’ strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%). EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. CONCLUSIONS: Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. TRIAL REGISTRATION: http://ClinicalTrials.gov identifier NCT01521546. Registered 26 January 2012. BioMed Central 2017-02-20 /pmc/articles/PMC5319045/ /pubmed/28219442 http://dx.doi.org/10.1186/s13023-017-0590-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Raman, Subha V.
Hor, Kan N.
Mazur, Wojciech
He, Xin
Kissel, John T.
Smart, Suzanne
McCarthy, Beth
Roble, Sharon L.
Cripe, Linda H.
Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial
title Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial
title_full Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial
title_fullStr Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial
title_full_unstemmed Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial
title_short Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial
title_sort eplerenone for early cardiomyopathy in duchenne muscular dystrophy: results of a two-year open-label extension trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319045/
https://www.ncbi.nlm.nih.gov/pubmed/28219442
http://dx.doi.org/10.1186/s13023-017-0590-8
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