Metabolic Modulators May Have Limited Use in Nonobstructive Hypertrophic Cardiomyopathy

Metabolic modulators such as trimetazidine have limited use in patients with nonobstructive hypertrophic cardiomyopathy (HCM), according to a randomized, placebo-controlled, double-blind clinical study published in JAMA Cardiology.¹

Patients with HCM experience left ventricular hypertrophy unexplained by loading conditions, which may cause exertional symptoms that can be treated with drugs or septal reduction.² However, there is conflicting evidence regarding therapy with inhibitors of myocardial fatty acid metabolism in these patients as their use is often limited by adverse effects or lack of clinical efficacy.

Therefore, researchers in London sought to determine the effects of oral therapy with trimetazidine, a direct inhibitor of fatty acid b-oxidation that has been shown to be safe and well tolerated, on exercise capacity in patients with symptomatic nonobstructive HCM.¹

Patients were between 24 and 74 years old, noncompliant with drug therapy, and had symptomatic HCM (New York Heart Association class ³2) 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.

Twenty-six patients were treated with 20 mg trimetazidine 3 times daily, and 23 patients received placebo. After 3 months, the researchers found that trimetazidine did not improve exercise capacity.

Patients in the trimetazidine group walked 38.4 meters less than patients in the placebo group and peak oxygen consumption was 1.35 mL/kg/minute lower in the trimetazidine group.

The authors concluded that, “Trimetazidine therapy does not improve exercise capacity in symptomatic patients with nonobstructive HCM.”¹ Thus, the therapeutic role for metabolic modulators has not been confirmed and pharmacologic therapy for this disease remains limited.

References

1. Coats CJ, Pavlou M, Watkinson OT, et al. Effect of trimetazidine dihydrochloride therapy on exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy: a randomized clinical trial [published online February 6, 2019]. JAMA Cardiol. doi:10.1001/jamacardio.2018.48472.
2. Elliott PM, Anastasakis A, Borger MA, et al; Authors/Task Force members. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733-2779.