Effects of trimetazidine on submaximal exercise test in patients with acute myocardial infarction

Background: It was demonstrated that the novel metabolic agent, trimetazidine, could lessen the incidence and severity of angina, whether used in monotherapy or combination. Although the animal studies demonstrated that trimetazidine reduces myocardial infarct size and improves recovery of mechanic function after ischemia, little is known on the potential benefits of trimetazidine in patients with acute myocardial infarction (AMI). The aim of this study was to evaluate the efficacy of trimetazidine on AMI by sub-maximal exercise test. Methods: A double-blind crossover trimetazidine versus placebo trial was carried out in 44 patients with AMI. Patients were randomly allotted into trimetazidine (23 patients) or placebo (21 patients) for 5 days and underwent an initial sub-maximal exercise test. Exercise tests according to the modified Bruce protocol were performed. Exercise end points included completion of stage II or 75% of maximum predicted heart rate whichever came first. An averaged 12-lead ECG was obtained at rest, every minute during exercise, at the onset of anginal symptoms, at the onset of 1-mm ST segment depression, at peak exercise and every 2-minute during recovery. After the initial exercise tests, study groups resumed the drugs in the opposite order for 4 to 5 days and underwent a second sub-maximal exercise test. Results: Exercise induced ST segment depression was noted in 17 patients (38.6%) receiving placebo. However, exercise induced ST-segment depression was observed in 8 patients (18.1%) taking TMZ. Positive exercise test results were significantly higher in placebo group than TMZ group (p=0.018). Additionally, trimetazidine prolonged the time to 1-mm ST-segment depression (6.1+/-0.5 vs 4.9+/-0.4, p<0.031) and exercise duration (7.2 +/- 0.9 vs 5.8 +/- 0.9, p<0.025). Conclusion: Trimetazidine therapy improves the exercise capacity and reduces evidence of ischemia derived from sub-maximal post-infarction exercise testing.