Heart Failure Drugs May Slow Decline in Muscular Dystrophy
Early intervention with commercially available heart failure drugs may slow the progressive decline in heart function for boys and young men with Duchenne muscular dystrophy (DMD) even before symptoms appear, according to a new study in The Lancet Neurology.
Predominantly affecting males, this genetic disorder causes rapid muscle weakening and degeneration—with a majority of patients developing heart or respiratory failure and only surviving into their 20s or early 30s.
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“These findings should motivate early cardioprotective treatment for DMD at a time when we can intervene to prevent progression and hopefully prevent longer-term complications of cardiomyopathy,” says lead study author Subha Raman, MD, MS, a cardiologist and professor at The Ohio State University Wexner Medical Center, in Columbus, OH.
Raman and her colleagues conducted the randomized, double-blind, placebo-controlled trial at three U.S. centers to determine whether the combination of eplerenone and either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) would decrease the progression of heart muscle disease, a leading cause of death in boys and young men with DMD. Prior lab findings had shown this combination reduced muscle damage and preserved function in animal models.
The researchers enrolled 42 boys, ages 7 and above, who had DMD and showed evidence of early heart muscle damage. In addition to background therapy with either ACE inhibitors or ARBs prescribed by their physicians, the participants were randomized to receive an oral dose of either 25 mg of eplerenone or a placebo for 1 year.
Based on cardiac MRI results, the team reported that there was significantly less decline in left ventricular circumferential strain after 12 months in the eplerenone treatment group compared to the placebo group. They also noted that at least 6 months of therapy was necessary to realize benefit.
While the study was not designed to look at the difference between the benefits of eplerenone combined with an ACE inhibitor vs. eplerenone combined with an ARB, Raman says, “One could expect a similar benefit from either since a) the distribution of ACE inhibitor vs. ARB use was similar in each arm and b) prior cardiomyopathy and heart failure trials have shown similar cardiac benefit using either ACE inhibitors or ARBs.”
This research was inspired by 26-year-old Ryan Ballou of Pittsburgh, a young man with DMD. In order to raise awareness and funding for Raman’s research of heart disease in muscular dystrophy patients, he and his father started BallouSkies, which was the primary financial supporter of this clinical study.
“This research progressed much faster thanks to their support,” Raman said in a press release. “The work we have accomplished in just a few years would have taken a decade or more if we had to seek funding from traditional grant mechanisms alone.”
The authors concluded: “Early use of available drugs warrants consideration in this population at high risk of cardiac death, but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy.”
Raman and her team will be starting a trial that will compare spironolactone vs. eplerenone in boys with DMD and preserved ejection fraction, with enrollment expected to begin in early 2015.
—Colleen Mullarkey
Reference
Raman SV, Hor KN, Mazur W, et al. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurology. 29 December 2014 [epub ahead of print].