Trimetazidine: a metabolic agent for the treatment of stable angina

It has been recently demonstrated that trimetazidine, known for years to be an effective antianginal agent, shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. By decreasing fatty acid oxidation, trimetazidine stimulates glucose utilization, restoring coupling between glycolysis and carbohydrate oxidation and leading to adenosine triphosphate production with lesser oxygen consumption. The antianginal properties of this agent are independent of haemodynamic changes, and dramatically improve recovery of mechanical function after ischaemia. Several studies have tested the efficacy of trimetazidine and have demonstrated this agent to be at least as effective as and better tolerated than haemodynamic agents. In stable effort angina, trimetazidine improves exercise tolerance and elevates the ischaemic threshold to an extent comparable with beta-blockers and calcium channel blockers. The combination of trimetazidine and a beta-blocker appears more effective than the combination of nitrates and a beta-blocker, and the addition of trimetazidine improves symptoms in patients resistant to diltiazem. The cardioprotective effects of trimetazidine have been recently confirmed in human ischaemia-reperfusion, including patients undergoing percutaneous coronary artery revascularization and bypass surgery with cardioplegic arrest. A new modified-release (MR) formulation of trimetazidine will shortly be introduced. A twice-daily regimen of these new MR tablets has been shown to be bioequivalent to the thrice-daily regimen of the previous formulation, and has been clinically tested in patients with stable angina pectoris resistant to beta-blockers. In a multicentre, international, double-blind, randomized, placebo-controlled study, the addition of trimetazidine MR tablets twice daily to atenolol 50 mg significantly prolonged the time to 1 mm ST depression and the time to onset of angina, with a favourable safety profile. The clinical safety of this new formulation has been confirmed in a double-blind, placebo-controlled study enrolling 234 elderly patients treated for 1 year. Safety and efficacy of trimetazidine MR promise to expand the role of metabolic agents for the treatment of ischaemic heart disease.