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

Subha V Raman,Sharon L Roble,Kan N Hor,Wojciech Mazur,John T Kissel,Linda H Cripe,Beth Mccarthy,Suzanne Smart,Xin He

doi:10.1186/s13023-017-0590-8

Abstract

BackgroundCardiomyopathy 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.ResultsEleven 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.ConclusionsEplerenone 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 registrationhttp://ClinicalTrials.gov identifier NCT01521546. Registered 26 January 2012.

Highlights

Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD)
In a recently-published randomized, double-blind 12-month clinical trial, we demonstrated that adding the available mineralocorticoid receptor antagonist drug eplerenone to background therapy was superior to placebo in boys with DMD and preserved ejection fraction (EF) in attenuating decline of cardiac function [9]
Similar patterns of change were observed in late gadolinium enhancement cardiac magnetic resonance (LGE) over the extension period in 12 months and in 24 months. In this 24-month open label extension study, we found a striking benefit on cardiac function in young boys with DMD

Summary

Introduction

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. In a recently-published randomized, double-blind 12-month clinical trial, we demonstrated that adding the available mineralocorticoid receptor antagonist drug eplerenone to background therapy was superior to placebo in boys with DMD and preserved EF in attenuating decline of cardiac function [9]. In this open-label extension study, we tested the hypothesis that eplerenone would have a durable benefit on cardiac function preservation

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