Effect of Trimetazidine Dihydrochloride Therapy on Exercise Capacity in Patients With Nonobstructive Hypertrophic Cardiomyopathy A Randomized Clinical Trial
Effect of Trimetazidine Dihydrochloride Therapy on Exercise Capacity in Patients With Nonobstructive Hypertrophic Cardiomyopathy A Randomized Clinical Trial
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DOI：
10.1001/jamacardio.2018.4847
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发表时间：
2019-03-01
期刊：
影响因子：
24
通讯作者：
Elliott, Perry M.
中科院分区：
文献类型：
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作者：
Coats, Caroline J.;Pavlou, Menelaos;Elliott, Perry M.
重要性肥厚型心肌病会导致患者出现限制性症状，部分原因是心肌能量利用效率低下。非梗阻性肥厚型心肌病患者使用心肌脂肪酸代谢抑制剂治疗存在相互矛盾的证据。目的确定曲美他嗪（一种脂肪酸β-氧化的直接抑制剂）口服治疗对症状性非梗阻性肥厚型心肌病患者运动能力的影响。设计、设置和参与者2012年5月31日至2014年9月8日在英国伦敦大学学院伦敦医院心脏医院进行了一项双盲临床试验。该试验纳入了51例药物难治性症状性（纽约心脏协会分级>= 2）患者，年龄24 - 74岁，最大左心室流出道压差50 mm Hg或更低，运动时峰值耗氧量为年龄和性别预测值的80%或更低。从2016年3月1日至2018年7月4日进行了统计分析。干预参与者被随机分配到曲美他嗪，20毫克，每日3次（n = 27）或安慰剂（n = 24）为3 months.Main结果和措施的主要终点是峰值氧消耗量在直立自行车测力计。次要终点为6分钟步行距离、生活质量（明尼苏达心力衰竭生活问卷）、室性异位搏动频率、舒张功能、血清N末端脑钠肽前体水平和肌钙蛋白T水平。结果49名接受曲美他嗪（n = 26）或安慰剂（n = 23）并完成研究的参与者中，34名（70%）为男性;平均（SD）年龄为50（13）岁。曲美他嗪治疗没有改善运动能力，在校正基线步行距离测量值后3个月，曲美他嗪组患者比安慰剂组患者步行少38.4 m（95%CI，5.13 - 71.70 m）。调整基线值后，干预组3个月后的峰值耗氧量降低了1.35 mL/kg/min（95%CI，-2.58 to -0.11 mL/kg/min; P =.03）。结论和相关性在非梗阻性肥厚型心肌病有症状的患者中，曲美他嗪治疗不能改善运动能力。这种疾病的药物治疗仍然有限。
IMPORTANCE 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.OBJECTIVE To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid beta-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. INTERVENTIONS Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months.MAIN OUTCOMES AND MEASURES The primary end pointwas 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. RESULTS 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 38.4m(95% CI, 5.13 to 71.70m) 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.CONCLUSIONS AND RELEVANCE In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited.