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Randomized Controlled Trial
. 2025 Mar;32(3):e70097.
doi: 10.1111/ene.70097.

Preventing Cardiomyopathy in Duchenne Muscular Dystrophy: Long-Term Follow-Up of Patients in the Randomised, Placebo-Controlled Drug-Trial of Perindopril and Bisoprolol

John P Bourke  1   2 , Andrew Bryant  3 , Gregory Landon  4 , Alexis Burn  5 , Stefan Spinty  6 , Ros Quinlivan  7 , Zoya Alhaswani  8 , Thomas Chadwick  3 , Francesco Muntoni  4 , Michela Guglieri  2 ; DMD Heart Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Preventing Cardiomyopathy in Duchenne Muscular Dystrophy: Long-Term Follow-Up of Patients in the Randomised, Placebo-Controlled Drug-Trial of Perindopril and Bisoprolol

John P Bourke et al. Eur J Neurol. 2025 Mar.

Abstract

Introduction: It is uncertain whether using cardiac drugs prophylactically in combinations for DMD is better than ACE-inhibitor alone. Our previous study showed no differences in left ventricular function between perindopril-bisoprolol and matched placebo after 36 months.

Methods: This study aimed to determine whether heart measures diverged after 60-month total follow-up. All participants had commenced open-label perindopril and bisoprolol when the original study ended. All were reconsented for access to heart measures, undertaken as part of their clinical care. The primary outcome was the change in echo-measured ventricular ejection fraction from baseline according to original randomization.

Results: Of 75 participants reported originally, 65 (aged 16 ± 2.5 years) were re-recruited and had data for analysis. Adjusted primary outcomes included 44 participants (original arms: 'active' 21; 'placebo' 23), 48 for secondary outcomes, and 65 for 'headcount' analysis of those with ventricular dysfunction. Absolute LVEF% values reduced in both groups ('active': 62.5% ± 5.6% to 53.8% ± 4.0%; 'placebo': 60.6% ± 4.9% to 50.4% ± 8.5%). Despite trends favoring earlier introduction of therapy, change from baseline was similar between groups (adjusted mean difference: -7.7 (95% CI -16.4 to1.0%)). However, more in the 'placebo' arm had died, had reduced LVEF%, and were taking additional heart medications.

Conclusion: While some patients may have benefited from 'early' (active) as opposed to 'delayed' (placebo) initiation of perindopril and bisoprolol, group-mean ventricular function did not differ between study arms after 60 months. Small numbers, absence of a control group, insensitivity of echo-ejection fraction, and additional drug use probably prevented divergence between groups.

Keywords: ACE‐inhibitor; DMD; beta‐blocker; cardiomyopathy prevention; heart medications; prophylaxis.

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Conflict of interest statement

Study Approval Statement: This study protocol was reviewed and approved by the London—Brent Research Authority [ID 269110; 09825], was registered with ISRCTN (registration number: 43827539) and Newcastle upon Tyne NHS Foundation Trust was the study sponsor (Joint Research Office: trust.r&d@nuth.nhs.uk).

John P. Bourke organisational grant from Duchenne UK to conduct this study. DMC participation fees from Sarepta Therapeutics; Travel support from Sarepta Therapeutics; consulting and advisory board fees from Sarepta Therapeutics, Pfizer, and the Esperare Foundation. Andrew Bryant (statistician) no conflicts of interest to declare. Gregory Landon no conflicts of interest to declare. Alexis Burn (trial manager) no conflicts of interest to declare. Stefan Spinty no conflicts of interest to declare. Ros Quinlivan reports receiving lecturing honoraria from PTC Bio, Sanofi‐Genzyme, Sarepta Therapeutics, Santhera, Roche, and Biogen; DMC participation fees from Roche, TRiNDs, Astellas, PTC Bio, Santhera, and Sarepta Therapeutics. Zoya Alhaswani reports travel support grant from Roche (unrelated to submitted work). Thomas Chadwick (statistician) no conflicts of interest to declare. Francesco Muntoni reports grants from Sarepta Therapeutics and Muscular Dystrophy UK; consulting fees from Roche and PTC; Travel support from Sarepta Therapeutics and Roche; DMC participation payments from Pfizer. Michela Guglieri reports acting as chair for a study sponsored by ReveraGen (no financial benefits); research collaborations with ReveraGen, Sarepta Therapeutics, and Edgewise; acting as CI/PI for clinical trials sponsored by Dyne, Pfizer, Italfarmaco, Edgewise, Roche, Santhera, ReveraGen, and Dynacure; participating in advisory boards for Pfizer, NS Pharma, Dyne (consultancies through Newcastle University); and receiving speaker honoraria from Sarepta, Italfarmaco, Novartis, Roche, and Dyne.

Figures

FIGURE 1
FIGURE 1
Participant flow through original and follow‐up phases of the study.
See this image and copyright information in PMC

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References

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