Effects of Trimetazidine on Myocardial Perfusion and the Contractile Response of Chronically Dysfunctional Myocardium in Ischemic Cardiomyopathy

Abstract

The aim was to assess the long-term effect of trimetazidine on myocardial perfusion, using gated single photon emission computerized tomography (SPECT). 200 patients (aged 54.7 ² 12 years) with ischemic left ventricular dysfunction (LVD) and multivessel coronary artery disease were randomized to receive trimetazidine 20mg three times daily or a placebo for 24 months. At baseline and after 24 months of treatment, all patients underwent a symptom-limited cardiopulmonary exercise test concluded by the injection of ^99mTc-MIBI (technetium-99m methoxy-isobutyl-isonitrile). Imaging of post-stress gated SPECT and resting gated SPECT were performed. Standard antianginal therapy was interrupted for 48 hours (nitrates for 6 hours) before the exercise tests and resumed immediately after testing. On initial evaluation, summed stress and rest scores (SSS and SRS, respectively), systolic wall thickness (SWT), and wall motion score index (WMI), heart rate, SBP, and rate pressure product were similar at rest and peak exercise in both groups. After 24 months, 91 % of patients in the trimetazidine group versus 22% in the placebo group showed a significant decrease of the frequency of anginal episodes per week (3.9 vs 5.7, p < 0.01). Weekly nitroglycerin (glyceryl trinitrate) tablet consumption was significantly lower with trimetazidine than with placebo at endpoint (2.3 ² 0.8 vs 6.1 ² 1.6, p < 0.01). This was supported by perfusion SPECT data. Compared with baseline values, SSS and SRS were significantly reduced with trimetazidine (from 19.8 ² 7.7 to 11.2 ² 6.1, p < 0.00001 and from 12.4 ² 8.7 to 5.8 ² 3.3, p < 0.00001, respectively). There was a nonsignificant decrease from baseline values in both SRS and SSS with placebo group (from 11.9 ² 8.3 to 11.2 ² 7.4 and 18.1²6.3 to 17.9 ² 9.2, respectively). Duration of peak exercise increased significantly from baseline values with trimetazidine (from 4.6 to 5.8 minutes, p < 0.01) but not with placebo (from 5.4 to 5.8 minutes). Accordingly, mean maximum work at peak exercise improved by 1.2 metabolic equivalents with trimetazidine. This was proved by gated SPECT with an increase in SWT score of 89.5% (p < 0.00001) and in ejection fraction of 23% with trimetazidine (p < 0.001) without significant changes in hemodynamic parameters. Trimetazidine improves ischemic attacks in patients with ischemic cardiomyopathy, clinically and objectively as seen in gated SPECT myocardial perfusion. The improvement in myocardial function with trimetazidine was not accompanied by hemodynamic changes.