Duchenne Muscular disease (DMD) is an inherited disorder related to a mutation in the dystrophin gene on the X chromosome. The clinical presentation of DMD includes constant myocardial involvement and progressive muscle weakness. Left ventricular (LV) systolic dysfunction typically develops after 10 years. This feature results in mortality in nearly 50% of patients.

Experimental research suggests angiotensin converting enzyme (ACE) inhibitors would exert a beneficial effect when used before onset of LV dysfunction. Therefore, investigators sought to determine whether early ACE inhibitor treatment would be protective against LV dysfunction in young DMD patients with normal LV ejection fraction.

Dr. Becana and colleagues conducted a 2-part study in children with genetically proven DMD and an ejection fraction greater than 55%. The first part of this study was a multicenter, controlled, randomized, double-blind trial of perindopril 2-4 mg/day for 3 years. In the second part, subjects continued on open-label perindopril for an additional 24 months. Investigators measured radionuclide LV ejection fraction at baseline and periodically throughout the study (6 evaluations in 60 months). No patient received any concomitant treatment.

Investigators enrolled 60 children in the first part of the study. Of these patients, 46 entered the second phase of the study. There were no significant differences in clinical or demographic characteristics at the beginning of the study. The mean age was approximately 11 years.

At baseline, the LV ejection fraction was 64.6% in the perindopril group and 65.4% for placebo. At the end of the first part of the study (24 months), LV ejection fraction was 59.6% for perindopril and 64.5% for placebo (p = 0.114).

At 24 months, 1 patient in the placebo group had a LV ejection fraction less than 45%, compared with none in the perindopril group. However, at 60 months, 6 placebo-treated patients (26%) had LV ejection fraction less than 45%, compared with only 1 perindopril-treated patient (4%). This difference was statistically significant (p = 0.0319).

Investigators documented no serious adverse events in the perindopril treatment group. In the placebo group, there were 2 patients experiencing serious adverse events (disseminated intravascular coagulation in one, and rash/edema in the other). There was no difference in incidence of minor adverse events between perindopril and placebo.

These findings demonstrate that reduction in LV ejection fraction is very common in young DMD patients. These patients appear to tolerate perindopril treatment well. The study results suggest early treatment with perindopril may delay the onset of deterioration in LV ejection fraction.