Bourke, John PWatson, GillianSpinty, StefanBryant, AndrewRoper, HelenChadwick, ThomasWood, RuthMcColl, ElaineBushby, KateMuntoni, FrancescoGuglieri, Michela2024-10-292024-10-292020-12-03Bourke JP, Watson G, Spinty S, Bryant A, Roper H, Chadwick T, Wood R, McColl E, Bushby K, Muntoni F, Guglieri M; DMD Heart Study Group. Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial. Neurol Clin Pract. 2021 Oct;11(5):e661-e668. doi: 10.1212/CPJ.0000000000001023.2163-04022163-093310.1212/CPJ.000000000000102334840880http://hdl.handle.net/20.500.14200/6282Objective: To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD) compared with placebo. Methods: This multicenter, parallel group, 1:1 patient randomized, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of left ventricular (LV) function, electrocardiogram, and adverse event reporting were performed 6 monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the National Research Ethics Service Committee East Midlands-Derby. Results: Eighty-five boys were recruited (76% on steroid therapy) and randomized to combination heart drugs or matched placebo. Group change in left ventricular ejection fraction (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 treatment arms over repeated assessments (analysis of variance) 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 Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function.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-month treatment. Classification of evidence: This study provides Class I evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.en© 2021 American Academy of Neurology.NeurologyDiseases & disorders of the nervous system (e.g. Parkinson's)PaediatricsArticle