University College London Institute of Cardiovascular Science, London, United Kingdom.
Queen Elizabeth University Hospital, Glasgow, United Kingdom.
JAMA Cardiol. 2019 Mar 1;4(3):230-235. doi: 10.1001/jamacardio.2018.4847.
Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy.
To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid β-oxidation, on exercise capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy.
DESIGN, SETTING, AND PARTICIPANTS: This randomized, placebo-controlled, double-blind clinical trial at The Heart Hospital, University College London Hospitals, London, United Kingdom was performed between May 31, 2012, and September 8, 2014. The trial included 51 drug-refractory symptomatic (New York Heart Association class ≥2) patients aged 24 to 74 years with a maximum left ventricular outflow tract gradient 50 mm Hg or lower and a peak oxygen consumption during exercise of 80% or less predicted value for age and sex. Statistical analysis was performed from March 1, 2016 through July 4, 2018.
Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months.
The primary end point was peak oxygen consumption during upright bicycle ergometry. Secondary end points were 6-minute walk distance, quality of life (Minnesota Living with Heart Failure questionnaire), frequency of ventricular ectopic beats, diastolic function, serum N-terminal pro-brain natriuretic peptide level, and troponin T level.
Of 49 participants who received trimetazidine (n = 26) or placebo (n = 23) and completed the study, 34 (70%) were male; the mean (SD) age was 50 (13) years. Trimetazidine therapy did not improve exercise capacity, with patients in the trimetazidine group walking 38.4 m (95% CI, 5.13 to 71.70 m) less than patients in the placebo group at 3 months after adjustment for their baseline walking distance measurements. After adjustment for baseline values, peak oxygen consumption was 1.35 mL/kg per minute lower (95% CI, -2.58 to -0.11 mL/kg per minute; P = .03) in the intervention group after 3 months.
In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited.
ClinicalTrials.gov identifier: NCT01696370.
重要性：肥厚型心肌病会导致患者出现限制症状，部分原因是心肌能量利用效率低下。对于非梗阻性肥厚型心肌病患者，使用脂肪酸代谢抑制剂进行治疗的证据存在冲突。
目的：确定口服曲美他嗪（一种脂肪酸β氧化的直接抑制剂）治疗有症状的非梗阻性肥厚型心肌病患者的运动能力的效果。
设计、设置和参与者：这是一项在英国伦敦大学学院附属医院心脏医院进行的随机、安慰剂对照、双盲临床试验，于 2012 年 5 月 31 日至 2014 年 9 月 8 日进行。该试验纳入了 51 名药物难治性（纽约心脏协会[NYHA]心功能分级≥2 级）、有症状（静息状态下左心室流出道最大压力阶差≤50mmHg 或运动时峰值耗氧量较预测值降低 80%）的 24 至 74 岁患者，这些患者存在最大左心室流出道梯度且峰值耗氧量较低。统计分析于 2016 年 3 月 1 日至 2018 年 7 月 4 日进行。
干预措施：参与者被随机分配至曲美他嗪组（20mg，每日 3 次，n=27）或安慰剂组（n=24），接受为期 3 个月的治疗。
主要终点和次要终点：主要终点为直立位自行车运动时的峰值耗氧量。次要终点包括 6 分钟步行距离、生活质量（明尼苏达州心力衰竭生存质量问卷）、室性异位搏动频率、舒张功能、血清 N 端脑利钠肽前体水平和肌钙蛋白 T 水平。
结果：在接受曲美他嗪（n=26）或安慰剂（n=23）治疗并完成研究的 49 名参与者中，34 名（70%）为男性；平均（SD）年龄为 50（13）岁。与安慰剂组相比，曲美他嗪组患者在 3 个月时的步行距离减少了 38.4m（95%CI，5.13 至 71.70m；调整基线步行距离测量值后），运动能力并未得到改善。调整基线值后，干预组的峰值耗氧量降低了 1.35mL/kg/min（95%CI，-2.58 至-0.11mL/kg/min；P=0.03）。
结论：在有症状的非梗阻性肥厚型心肌病患者中，曲美他嗪治疗并不能改善运动能力。这种疾病的药物治疗仍然有限。
试验注册：ClinicalTrials.gov 标识符：NCT01696370。
