In 2001, Saito et al. (25) evaluate the efficacy of oral carvedilol (10.1-40.3 μg/kg/day) for 6 months in 4 DMD patients who had elevated plasma atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP), and a low ejection fraction (EF< 40%) in echocardiography. The values did not change significantly compared with controls. Clinical symptoms also did not change in either group. Inhibitors,research,lifescience,medical They conclude that carvedilol therapy did not change the left ventricular dysfunction in DMD. However carvedilol therapy can be safe for patients with dilated

cardiomyopathy associated with muscular dystrophy, even producing a modest improvement in systolic and diastolic function (26). Combination of therapy It has been reported that the Inhibitors,research,lifescience,medical combination of an ACEinhibitor and a beta-blocker has additive effects in patients with congestive heart failure. Such an approach has been extended to Duchenne muscular dystrophy patients with left ventricular dysfunction in order to assess whether this combination was associated with long term survival of DMD patients with dilated cardiomyopathy. In 1999, Ishikawa et al. (27) reported the effectiveness of the combination of Inhibitors,research,lifescience,medical ACEI and beta-blockers in 11 DMD patients with symptomatic heart AZD8931 in vivo failure for relief of symptoms and decrease of activated neuroendocrine

level during 5-year follow up. In 2006, Kajimoto et al. (28) confirmed the beneficial effects of the association beta-blocker carvedilol/ACEI on ventricular function in Inhibitors,research,lifescience,medical 13 patients with muscular dystrophy compared with the ACEI only. In fact the combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS), while in the ACEI group, there was no significant change in LVFS. Left ventricular enddiastolic dimension increased in the

ACEI group, but not in the carvedilol/ACEI group. Ten years later, Ogata et al. (29) studied the long term efficacy Inhibitors,research,lifescience,medical second of an ACEI and a beta-blocker in 52 DMD patients with reduced LVEF, with [12] or without [40] symptoms of heart failure. They showed that 5-year and 7-year survival rates of symptomatic patients were 81 and 71% respectively. Survival rate became 0 at 10,9 years. In the prevention group (asymptomatic patients) 5- and 7-year survival rates were 97 and 84% respectively, and 10-year survival rate was 72%. The beneficial effects of the combined ACEIs and beta- blockers therapy has been observed in DMD patients, with both gene deletions or point-mutations (30). Recent papers (31, 32) confirm that the use of ACEIs and beta-blockers in patients with DMD reverse congestive heart failure signs and symptoms, delay regression of left ventricular disfunction and improve systolic function.