Cardiac dysfunction is a common cause of death for individuals with Duchenne muscular dystrophy. Early detection and management of cardiac abnormalities in these boys could dramatically improve their quality of life and survival.
In Lancet Neurology,
Raman et al report on a randomized, double-blind, placebo-controlled trial that tested the efficacy of the aldosterone antagonist eplerenone (Inspra) in boys with Duchenne muscular dystrophy. Boys received eplerenone (25mg) or placebo every other day for the first month then once daily if their potassium concentration at 1 month was within the accepted range of 5.5 nmol/L or less. In total, 40 boys completed the 12 month study (20 in the eplerenone group and 20 in the placebo group).
The study found that after 12 months, the decline in left ventricular circumferential strain (Ecc) was less pronounced in those who received eplerenone than in those who received placebo (median change Ecc 1.0 [IQR 0.3–2.2] vs 2.2 [1.3–3.1]; P
=.020). Cystatin C concentrations remained normal in both groups, and all non-hemolyzed blood samples showed normal potassium concentrations. One 23-year-old patient in the placebo group died of fat embolism, and another patient in the placebo group withdrew from the trial to address long-standing digestive issues. All other adverse events were mild: short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone, flushing occurred in one patient given placebo, and anxiety occurred in another patient given placebo.
The boys in the study were mostly teenagers with median age of 14.5 years in the eplerenone group (range 12-18.5 years) and 15.0 years in the placebo group (11-19 years). All patients were also receiving an ACE inhibitor or angiotensin receptor blocker (ARB) and approximately 40% were taking beta blockers at the time of the study. Half (50%) of the boys in the eplerenone group were ambulatory compared to 36% in the placebo group.
The authors of the study concluded:
Our findings suggest that early treatment with eplerenone attenuates decline in cardiac function, which is a leading cause of death in Duchenne muscular dystrophy. Subsequent trials should compare various mineralocorticoid receptor antagonists and dosing regimens with differing background therapies. Future studies should also examine the clinical effect on skeletal muscle as well as genetic and other modifiers that might affect skeletal versus myocardial response to treatment.
Raman SV, Hor KN, Mazur W, et al. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. [Epub ahead of print