John P Bourke1, Gillian Watson1, Stefan Spinty1, Andrew Bryant1, Helen Roper1, Thomas Chadwick1, Ruth Wood1, Elaine McColl1, Kate Bushby1, Francesco Muntoni1, Michela Guglieri1. 1. Department of Cardiology (JPB), Freeman Hospital, NUTH NHS Hospitals Foundation Trust; Clinical Trials Unit (MC, RW), Newcastle University, Newcastle upon Tyne; Department of Paediatric Neurology (SS), Alder Hey Children's NHS Foundation Trust, Liverpool; Population Health Sciences Institute (AB, TC, EM), Newcastle University, Newcastle upon Tyne; Department of Paediatrics (HR), Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust; John Walton Muscular Dystrophy Research Centre (KB, MG), Newcastle University and Newcastle upon Tyne, NHS Hospitals Foundation Trust, Newcastle upon Tyne; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, UK.
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 Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function.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.
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.
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