Modulation of metabolic changes in patients with heart failure by selective inhibition of 3-ketoacyl coenzyme A thiolase

A direct approach to manipulating cardiac energy metabolism consists of modifying substrate utilization by the heart. Pharmacological agents that directly inhibit fatty acid oxidation include inhibitors of 3-ketoacyl coenzyme A thiolase, the last enzyme involved in b-oxidation. The most extensively investigated agent of this group of drugs is trimetazidine. Clinical studies have shown that trimetazidine can substantially increase the ischemic threshold in patients with effort angina. However, the results of current research also support the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism by the use of trimetazidine could be an effective adjunctive treatment in patients with heart failure, in terms of improvement in left ventricular and endothelial function and glucose metabolism. The recent literature on the protective effects of this new class of drugs on left ventricular dysfunction is reviewed and discussed. Heart Metab. 2006;33:21‐24.