Early treatment with the aldosterone antagonist eplerenone (Inspra, Pfizer) plus an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) slows the progression of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD), a new randomized trial shows.
"Because of the safety and efficacy shown in this [study], I believe this approach is ready for thoughtful clinical use," Subha Raman, MD, cardiologist and professor at The Ohio State University Wexner Medical Center in Columbus, who led the study, told Medscape Medical News.
Boys with DMD and preserved ejection fraction but myocardial damage on late gadolinium enhancement cardiac MRI (LGE-CMR) "should be considered for this combination therapy," Dr Raman added.
The study was published online December 30 in Lancet Neurology.
New Standard of Care?
Participants included 42 boys and young men aged 7 years or older with DMD, myocardial damage on LGE-CMR, and left ventricular ejection fraction of at least 45% who were receiving ACEI or ARB therapy. They were randomly allocated to add eplerenone 25 mg or placebo orally every other day for the first month and once daily thereafter. All 20 boys in the eplerenone group and 20 of 22 in the placebo group completed the baseline, 6-month, and 12-month assessments, which included cardiac MRI.
At 12 months, the further decline from baseline in left ventricular circumferential strain, a sensitive and early marker of contractile dysfunction and the primary outcome, was significantly less in those who received eplerenone than in those who received placebo (median, 1.0% vs 2.2%; P = .020).
Left ventricular circumferential strain is "abnormal well before complications like congestive heart failure and fatal arrhythmias occur in DMD," Dr Raman notes in a statement. "By impacting this earliest detectable change in heart function, we expect and hope to see even greater benefits with longer-term follow-up of these patients. Slowing the progression of heart disease should translate into improved quality of life for affected individuals and their families," she added.
Eplerenone also attenuated the decline in left ventricular ejection fraction at 12 months (change, –1.8% vs –3.7% with placebo; P = .032). The researchers note that at least 6 months of eplerenone was needed to realize the cardiac benefits of eplerenone.
Concentrations of cystatin C, a noncreatinine measure of kidney function, and potassium remained normal in both groups. Adverse events were mild, the researchers say. One patient in the eplerenone group reported short-lived headaches coincident with seasonal allergies.
Cardiomyopathy is a leading cause of death in patients with DMD. The current study suggests that eplerenone, a drug with established effectiveness in other cardiac diseases, "can be repurposed to slow the genetically programed decline in cardiac function in boys with DMD," Dr Raman said.
"The big takeaway for clinicians reading this work is hopefully that early treatment, before complications like heart failure and sudden cardiac death become apparent and even before the pump function (ejection fraction) is significantly abnormal, is beneficial in this high risk population," she added.
Eplerenone "could quickly become standard of care for patients with DMD," Linda Cripe, MD, pediatric cardiologist and coinvestigator from Nationwide Children's Hospital in Columbus, Ohio, said in the statement.
Improve and Prolong Life?
In a Comment published with the study, Corrado Angelini, MD, IRCCS Fondazione San Camillo Hospital, Venice, Italy, notes that eplerenone lacks "important contraindications" and "could potentially improve and prolong the life" of boys with DMD.
"Future trials should investigate whether treatment of cardiomyopathy with eplerenone could benefit not only patients with Duchenne muscular dystrophy, but also those with severe cardiomyopathy associated with other muscular dystrophies, such as Becker muscular dystrophy, sarcoglycanopathies, or laminopathies," Dr Angelini says.
The study was supported by BallouSkies, Parent Project Muscular Dystrophy, US National Center for Advancing Translational Sciences, and the National Institutes of Health. Pfizer Pharmaceuticals provided eplerenone and matching placebo but had no active role in the study. Dr Raman receives research support through her institution from Siemens, a manufacturer of MRI equipment used in the study. The other authors and Dr Angelini have disclosed no relevant financial relationships.
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Cite this: Approved Cardiac Drugs Slow Cardiomyopathy in DMD - Medscape - Jan 05, 2015.