Preventing cardiomyopathy in DMD: A randomized, placebo-controlled drug-trial

Abstract Objective: To determine whether a combination of two heart medications would be tolerated and could prevent / delay the onset of cardiomyopathy in boys with DMD compared to placebo. Methods: This multi-centre, parallel group,1:1 patient randomised, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of LV-function, ECG and Adverse Event reporting were performed six-monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the NRES Committee East Midlands - Derby. Results: Eighty-five boys were recruited (76% on steroid therapy) and randomised to combination heart drugs or matched placebo. Group change in LVEF% at 36 months from baseline was -2.2 + 6.0% and -2.9 + 6.1% in active and placebo arms (adjusted mean difference: -2.1, 95% CI -5.2 to 1.1). There was no difference between arms over repeated assessments (ANOVA) up to 36 months (trial arms p = 0.53); arm-over-time (p = 0.44). Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV-function. Secondary outcomes did not differ between arms either. Thirty-six Serious Adverse Events occurred none due to cardiac events or trial medication. Conclusions: Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-months treatment. Classification of evidence: This study provides Class 1 evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.