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Abstract
Objective 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 Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function.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.
Footnotes
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
DMD Heart Study Group coinvestigators are listed in Appendix 2.
F. Muntoni and M. Guglieri are joint senior authors and contributed equally to the manuscript.
Study registration: DMD Heart Protection trial; EudraCT: 2007-005932-10 and ISRCTN 50395346.
Study Sponsor: NHS Hospitals Foundation Trust, UK (contact details: Newcastle Joint Research Office, Level 1 Regent Point, Gosforth, Newcastle upon Tyne NE3 3HD; Trust.R&D{at}nuth.nhs.uk). The study sponsor has not had any role in protocol design and/or in the reporting of findings, nor did it have ultimate authority over presentation of results.
Class of Evidence: NPub.org/coe
- Received June 28, 2020.
- Accepted November 6, 2020.
- © 2021 American Academy of Neurology
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