Metabolic management of ischemic heart disease: clinical data with trimetazidine

The metabolic management of heart disease represents a promising new strategy for ischemic syndromes. This review focuses on the clinical studies performed with trimetazidine, a cellular anti-ischemic agent, either as monotherapy or in combination with other drugs. Acute and chronic administration of trimetazidine significantly increased total work, exercise duration, and time to 1-mm ST segment depression, without any change in heart rate, systolic blood pressure, or rate-pressure product at the same workload, as compared with placebo. Chronic administration studies have been performed comparing the anti-ischemic effects of trimetazidine with nifedipine or propranolol in patients with chronic stable angina. In these studies, the number of anginal attacks was significantly decreased in all groups. Ergometric results showed that trimetazidine increased duration of exercise, time to 1-mm ST segment depression, time to angina, and decreased ST segment depression at peak exercise similarly to propranolol or nifedipine treatment. Rate-pressure product at the same workload remained unchanged in the patients treated with trimetazidine in comparison with baseline treatment, suggesting no effect of the drug on oxygen demand, whereas it was decreased during treatment with nifedipine and propanolol, because of the hemodynamic activity of these drugs. The therapeutic value of adding trimetazidine to either calcium antagonists or beta blockers in patients with ischemic heart disease has also been demonstrated. Unlike classic anti-ischemic agents, treatment with trimetazidine is not accompanied by any modification in hemodynamic parameters, confirming the experimental data showing a unique mechanism of action via a direct effect on the ischemic myocardium.