The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of glucose homeostasis are consistently present in patients with IHD, definitely contributing to the progression of the primary disease. If not adequately treated, in most patients glucose metabolism abnormalities will heavily contribute to the occurrence of complications, of whom severe left ventricular dysfunction is at present one of the most frequent and insidious. Apart from a meticulous metabolic control of frank diabetes, special attention should be also paid to insulin resistance, a condition that is generally underdiagnosed as a distinct clinical entity. An important metabolic alteration in diabetic patients is the increase in free fatty acid concentrations and the increased muscular and myocardial free fatty acid uptake and oxidation. The increased uptake and utilization of free fatty acid and the reduced utilization of glucose as source of energy during stress and ischemia are responsible for the increased susceptibility of the diabetic heart to myocardial ischemia and to a greater decrease of myocardial performance for a given amount of ischemia compared to non diabetic hearts. In order to shift cardiac metabolism from FFA to preferential glucose utilization, the use of FFA inhibitors has been advocated. Among FFA inhibitors etomoxir, perhexiline, oxfenicine and trimetazidine have been evaluated. Among them, trimetazidine, specifically a 3-ketoacyl coenzyme A thiolase inhibitor, has been shown to improve overall glucose metabolism in IHD patients with diabetes and left ventricular dysfunction. The observed combined beneficial effects of FFA inhibitors on myocardial ischemia, left ventricular function and glucose metabolism, represent an additional advantage of these drugs, especially when myocardial and glucose metabolism abnormalities coexist. In this paper, the recent literature on the beneficial therapeutic effects of FFA oxidation inhibitors on myocardial ischemia, left ventricular dysfunction and glucose metabolism in patients with ischemic heart disease and abnormalities of carbohydrate metabolism is reviewed and discussed.
ASJC Scopus subject areas
- Drug Discovery