New pharmacological targets in the treatment of heart failure: Inhibition of free fatty oxidation by trimetazidine

Heart failure may promote alterations of cardiac metabolism, resulting in the depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include pharmacological agents that directly inhibit fatty acid oxidation. Trimetazidine (Vastarel® MR) appears to be the most investigated agent in this setting. The results of current research support the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure. More specifically, very recent meta-analyses have confirmed that the additional use of trimetazidine in heart failure patients may yield a significant protective effect for all-cause mortality, cardiovascular events and hospitalization for cardiac causes, improve clinical symptoms and cardiac function, and simultaneously ameliorate left ventricular remodeling. Certainly, in order to clarify the exact therapeutic role of metabolic therapy in heart failure, a large multicenter randomized controlled trial should be performed.