Effect of trimetazidine dihydrochloride therapy on exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy: A randomized clinical trial

Caroline J. Coats, Menelaos Pavlou, Oliver T. Watkinson, Alexandros Protonotarios, Linda Moss, Rebecca Hyland, Khadija Rantell, Antonis A. Pantazis, Maite Tome, William J. McKenna, Michael P. Frenneaux, Rumana Omar, Perry M. Elliott

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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 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.

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 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.

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 38.4 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.

Conclusions and Relevance: In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited.

Trial Registration: ClinicalTrials.gov identifier: NCT01696370.

Original languageEnglish
Pages (from-to)230-235
Number of pages6
JournalJAMA Cardiology
Issue number3
Early online date6 Feb 2019
Publication statusPublished - Mar 2019

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