Trimetazidine improves endothelial dysfunction in chronic heart failure: an antioxidant effect.

Aims: To determine whether trimetazidine (TMZ) improves the endothelium-dependent relaxation (EDR) in chronic heart failure (CHF) and whether this effect is associated with its antioxidant properties.

Methods And Results: We studied 51 patients (mean age 51.4 +/- 6 years) with CHF secondary to ischaemic cardiomyopathy (ejection fraction 32.5 +/- 4.5%). Plasma malondialdehyde (MDA) and lipid hydroperoxides (LOOHs) were measured from an antecubital vein on study entry and after a 4 week treatment with oral TMZ (20 mg tid) (group T, n = 23) or placebo (group C, n = 22) given randomly. Endothelium-dependent vasodilation of the radial artery (RA) was determined by intra-arterial infusion of acetylcholine (7.5, 15 and 30 microg/min). Patients receiving TMZ had an increased radial artery diameter (RAD) in response to each dose of acetylcholine infusion and a greater peak oxygen uptake (P < 0.01 vs. placebo). Plasma MDA and LOOHs levels were reduced at 4 weeks only in patients receiving TMZ (P < 0.001 for both vs. placebo). The improvement in ED-vasodilation was correlated with changes in peak VO(2) (r = 0.68; P = 0.0001), MDA (r = -0.61; P = 0.0002) and LOOHs (r = -0.59; P = 0.005).

Conclusion: TMZ improves the ED-relaxation in patients with ischaemic cardiomyopathy. The antioxidant properties of TMZ may play a role.