Partial inhibition of fatty acid β-oxidation with trimetazidine - a novel approach to the treatment of ischemic heart disease

Optimizing myocardial energy substrate metabolism represents a novel therapeutic intervention in the treatment of ischemic heart disease that can be a useful adjunct to traditional hemodynamic therapies. Specifically, the partial inhibition of fatty acid β-oxidation, and the concomitant, reciprocal increase in glucose oxidation, improves cardiac efficiency, and limits the deleterious effects of ischemia on cardiac function. Trimetazidine is a reversible inhibitor of 3-ketoacyl-CoA thiolase, the terminal enzyme of fatty acid β-oxidation. The antiischemic effects of trimetazidine are related to its ability to partially inhibit fatty acid β-oxidation, while indirectly stimulating glucose oxidation. These antiischemic effects of trimetazidine have been demonstrated in numerous experimental and clinical studies in diverse forms of ischemic heart disease ranging from angina to acute myocardial infarction, and heart failure. Thus the partial inhibition of fatty acid β-oxidation is a novel and viable therapeutic intervention to limit the deleterious effects of ischemic heart disease.