Effects of trimetazidine on myocardial perfusion and left ventricular systolic function in type 2 diabetic patients with ischemic cardiomyopathy

Aims: To determine whether short-term treatment with trimetazidine (TMZ), an antiischemic agent that directly inhibits fatty acid oxidation and results in stimulation of glucose oxidation, may improve myocardial perfusion and left ventricular systolic function in diabetic patients with ischemic cardiomyopathy. Methods and Results: We studied 34 clinically stable patients with type 2 diabetes mellitus (DM) and documented multivessel coronary artery disease (29 men and 5 women, mean age 54 +/- 9 years) with depressed systolic function (left ventricular ejection fraction 38 +/- 6%). Patients were randomized into two groups. One group received TMZ (20 mg tid) for 3 months (n = 19), while another group received a placebo during the same period (n = 15). On study entry and at 3 months, all patients underwent a gated Single Photon Emission Computed Tomography (SPECT) myocardial scintigraphy with a 2-day stress(Bruce)-rest protocol (500 MBq tetrofosmin). At 3 months, TMZ-treated patients had a significant improvement in systolic wall thickening (P < 0.05) and ejection fraction (P = 0.007) as compared with control patients. These effects were more marked in patients with more severe reversible perfusion defects on initial evaluation and were not associated with changes in myocardial defects (P = 0.38). Total exercise time was also improved in TMZ-treated patients (20.5%, P < 0.05 vs. controls). Conclusions: in diabetic cardiomyopathy, short-term TMZ improved left ventricular systolic function and functional capacity despite no change in myocardial perfusion. These benefits were more evident in patients with more severe perfusion defects on initial evaluation, suggesting that chronic myocardial ischemia is a requirement for the effects of TMZ on left ventricular systolic performance.