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

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.