Bourke John P, Watson Gillian, Spinty Stefan, Bryant Andrew, Roper Helen, Chadwick Thomas, Wood Ruth, McColl Elaine, Bushby Kate, Muntoni Francesco, Guglieri Michela
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.
Neurol Clin Pract. 2021 Oct;11(5):e661-e668. doi: 10.1212/CPJ.0000000000001023.
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.
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.
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 = 0.53); arm-over-time ( = 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 Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function.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.
Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-month treatment.
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.
与安慰剂相比，确定两种心脏药物联合使用是否能被患有杜氏肌营养不良症（DMD）的男孩耐受，并预防/延迟心肌病的发作。
这项多中心、平行组、1:1患者随机、安慰剂对照的培哚普利和比索洛尔预防性研究招募了5至13岁、心室功能正常的DMD男孩。每6个月对左心室（LV）功能、心电图和不良事件报告进行重复评估。主要结局是36个月后两组间射血分数的变化。该研究得到了东米德兰兹-德比国家研究伦理服务委员会的批准。
招募了85名男孩（76%接受类固醇治疗），并随机分为联合心脏药物组或匹配的安慰剂组。在36个月时，活性药物组和安慰剂组左心室射血分数（LVEF%）相对于基线的组内变化分别为-2.2%±6.0%和-2.9%±6.1%（调整后平均差异：-2.1，95%CI -5.2至1.1）。在长达36个月的重复评估中（方差分析），各治疗组之间没有差异（试验组 = 0.53）；组随时间变化（ = 0.44）。4名接受安慰剂治疗的参与者因LV功能恶化而退出，但接受活性治疗的参与者无人退出。次要结局在两组之间也没有差异。发生了36起严重不良事件，均与心脏事件或试验药物无关。
联合治疗耐受性良好。与之前的培哚普利预防性心脏研究一致，36个月治疗后没有证据表明联合治疗有组间获益。
本研究提供了I类证据，表明培哚普利-比索洛尔联合治疗耐受性良好，但在患有DMD的男孩中并未显著改变LVEF的下降。
