Trimetazidine MR improves survival of coronary patients

well designed clinical trials had shown the antiischemic and cardioprotective benefits of TMZ. The benefits of TMZ in reducing ischemia and improving cardiac function have a considerable potential for improving survival in those coronary patients with highest risk such as those with acute myocardial infarction or with heart failure. Given these results, large- scale, prospectively designed, randomized, double-blind trials are still required to clarify this question. Trimetazidine (1-(2, 3, 4- trimethoxybenzyl) piperazine dihydrochloride; TMZ) is a metabolic anti- ischemic agent, used both alone and in combination with hemodynamic antianginal drugs in the treatment of stable angina. Its cytoprotective effect comes from direct inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase (KAT). Trimetazidine optimizes cardiac metabolism by switching energy substrate preference from fatty-acid oxidation to glucose oxidation, which requires less oxygen to produce the same amount of adenosine triphosphate (ATP), providing energy required by the heart in ischemic conditions (1). This mechanism can protect the heart from many deleterious consequences of ischemia. Recently, a meta-analysis was done to evaluate the efficacy of trimetazidine monotherapy in the treatment of stable angina pectoris (2). This study concluded that trimetazidine significantly improved left ventricular ejection fraction (LVEF), with a mean increase of 6.88% (95% confidence interval (CI):5.50-8.25), and significantly reduced LV end-systolic volume (LVESV) and wall motion score index (WMSI). A recently published meta-analysis (3) to explore the role of trimetazidine in patients with heart failure also concluded that trimetazidine therapy was associated with a significant improvement in LVEF in patients with both ischemic and non-ischemic heart failure. With trimetazidine therapy, LVESV and New York Heart Association classification was improved (3). Surprisingly, trimetazidine had a significant protective effect for all- cause mortality (RR 0.29; 95% CI: 0.17-0.49; p<0.00001) and cardiovascular events and hospitalization. The following section summarizes some of important clinical evidences that suggested the role of trimetazidine in improving survival of coronary patients. Evidence in patients with ischemic cardiomyopathy A randomized, double-blind, placebo-controlled trial published in 1998 studied the effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease. In this study, oral trimetazidine could significantly improve left ventricular function, assessed by echocardiography, and helped to decrease severity of dobutamine-induced left ventricular dysfunction (4). Another randomized, double-blind, placebo-controlled trial was published in the European Heart Journal in 2001. This study demonstrated that oral trimetazidine could improve left ventricular contractile response of chronically dysfunctional myocardium assessed by low-dose dobuta- mine echocardiography in patients with ischemic cardiomyopathy (5). A randomized, double-blind, placebo-controlled study published in 2003 demonstrated beneficial effects of trimetazidine in diabetic patients with ischemic cardiomyopathy (6). This study showed that six