Trimetazidine Therapy in Coronary Artery Disease: The Impact on Oxidative Stress, Inflammation, Endothelial Dysfunction, and Long-Term Prognosis.

Abstract

In coronary artery disease (CAD), reduction of perfusion in coronary arteries is followed by increases of oxidative stress and decreases of adenosine triphosphate reserve. In this condition, trimetazidine (TMZ), a metabolic anti-ischemic agent, seems to be an ideal therapeutic agent because it increases mitochondrial adenosine triphosphate production. To evaluate the impact of TMZ on oxidative stress, inflammation, endothelial dysfunction, and long-term prognosis in CAD. Patients with CAD with symptoms not adequately controlled were enrolled consecutively for a period of 18 months. Five hundred seventy patients with CAD were enrolled in a prospective study and divided into 4 groups in relation with the type of CAD and the addition of TMZ to optimal medical therapy (OMT). The impact of TMZ added to OMT on oxidative stress (total antioxidant status, antioxidized low-density lipoprotein antibodies, and antimyeloperoxidase antibodies), endothelial dysfunction (flow-mediated dilatation and von Willebrand factor activity), and inflammation (C-reactive protein and fibrinogen) at 6 months and on long-term prognosis in CAD in comparison with OMT at 5 years of follow-up was evaluated. At 6 months, TMZ added to OMT significantly decreased the incidence of oxidative stress in CAD (P < 0.03) and reduced endothelial dysfunction and inflammation only in non-ST-elevation acute coronary syndrome (NSTE-ACS, P < 0.04). TMZ added to OMT with or without interventional/surgical vascularization led to decreased readmission for NSTE-ACS and heart failure (P < 0.05) in all patients with CAD and a significantly reduced incidence of cardiovascular death, acute myocardial infarction, and stroke (P < 0.05) in patients with NSTE-ACS at 5 years of follow-up. In patients with NSTE-ACS, TMZ added to OMT with or without interventional and/or surgical reperfusion reduced oxidative stress, endothelial dysfunction, inflammation, and major acute cardiovascular events, whereas in patients with chronic coronary syndrome, TMZ decreased oxidative stress and readmission for ACS and heart failure.