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Early ACE Inhibitor Tx Slows Muscular Dystrophy Heart Damage

Clicks:Updated:2016-12-09 09:12:46

Early treatment with an ACE inhibitor helps slow progression of myocardial damage in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), a randomized trial showed.

Among patients in the earliest stages of cardiomyopathy associated with the disease -- with myocardial fibrosis present on cardiac MRI but still preserved left ventricular ejection fraction (LVEF), enalapril (Vasotec) slowed progression of the myocardial fibrosis compared with no treatment over 2 years of follow-up (mean increase of 3.1% versus 10.0% as a percentage of LV mass, P=0.001).

After multivariate adjustment, ACE inhibitor therapy independently predicted decreased myocardial fibrosis progression over that period (coefficient -4.51, P=0.04), Carlos Eduardo Rochitte, MD, PhD, of the Heart Institute at the University of São Paulo, Brazil, and colleagues reported online in JAMA Cardiology.

"Currently, the therapeutic intervention with ACE inhibitors is initiated based on altered LVEF, which is a late finding in the myocardial damage cascade in muscular dystrophies," they concluded. "Our data suggest that ACE inhibitor therapy should start before the onset of LV dysfunction and when myocardial fibrosis becomes detectable by cardiovascular magnetic resonance."
Elizabeth M. McNally, MD, PhD, of Northwestern University in Chicago, agreed in an accompanying editor's note.

Together with other research showing eplerenone (Inspra) reduces LV strain defects in DMD, "these studies provide sound evidence for early intervention to prevent or slow cardiomyopathy progression with medical management," she wrote. And there may be implications beyond muscular dystrophy as well, McNally suggested. "With the increasing availability of genetic testing for dilated cardiomyopathy, there is now emerging a group of younger, gene mutation-positive individuals who are prone to developing cardiomyopathy and ultimately heart failure," she wrote. "Data are lacking on whether early treatment would similarly benefit this group, but the present investigation indicates that this issue should be addressed.

"As we move closer to using genetic signatures to identify individuals at risk and applying tailored therapy, we realize a goal of personalized medicine."

Rochitte's trial included 76 male patients, six of whom had BMD (8%), with a mean age of 13.1 years seen at two centers in Brazil. Myocardial fibrosis, present at baseline in 72%, independently predicted lower LVEF at follow-up (coefficient -0.16, P=0.03), and was associated with a higher rate of cardiovascular events (18.2% versus 0%, log-rank P=0.04).

Only the 42 patients (55%) with myocardial fibrosis and preserved LVEF were randomized to ACE inhibitor treatment with enalapril or not. The trial was not designed to be analyzed by intent-to-treat.

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