Focus on trimetazidine in acute coronary syndrome

Abstract

Trimetazidine is an anti-ischemic agent that acts at the cellular level by shifting the cardiac energy metabolism from β-oxidation of free fatty acids to the more efficient glucose oxidation. In patients with an acute myocardial infarction (AMI) who are treated with thrombolysis and/or a percutaneous coronary intervention (PCI), ischemia-reperfusion injury may occur after reestablishing myocardial blood supply to an ischemic region. In animal models of ischemia-reperfusion injury, trimetazidine markedly reduced casein kinase and lactate dehydrogenase activities and decreased the infarct size. In patients with an AMI, trimetazidine reduced the rate of any form of reperfusion arrhythmias, more so with potentially life-threatening arrhythmias. In the EMPI-FR study (European Myocardial Infarction Project – Free Radicals), in the subset of patients not receiving thrombolysis assessed as per-protocol analysis, there was an 11.9% and 13.8% risk reduction in 35-day mortality and in-hospital mortality, respectively, in patients receiving trimetazidine. More recently, it was shown that trimetazidine, as an adjunctive therapy to PCI, reduced myocardial damage and preserved left ventricular function more than PCI alone. In a large registry of patients with AMI, the use of trimetazidine was associated with significant reductions in all-cause mortality and combined major adverse cardiac events (MACE), a finding that was confirmed in the first meta-analysis to report these benefits in patients with AMI treated with trimetazidine, showing a 67% risk reduction for MACE, which was defined as the composite of death, recurrent nonfatal MI, target vessel revascularization, coronary artery bypass graft, recurrence of angina, and/or hospitalization for heart failure. L Heart Metab. 2018;75:22-27