Combination therapy of trimetaxidine with diltiazem in patients with coronary artery disease

Abstract

The efficacy of trimetazidine, an antianginal agent with a direct effect on ischemic myocardium, has been tested alone or in combination with β blockers or nifedipine. The combination with diltiazem, a widely used calcium antagonist, has not been studied. The aim of this study was to evaluate the potential benefit of oral trimetazidine (20 mg 3 times daily) in combination with oral diltiazem (60 mg three times daily). This was a multicenter, placebo-controlled study with a follow-up period of 6 months. Patients with stable angina and a positive exercise electrocardiogram before and after 15 days of diltiazem therapy were included. The 67 patients were randomized to diltiazem plus placebo (group I, 35 patients) and diltiazem plus trimetazidine (group II, 32 patients). Follow-up included a bicycle ergometer maximal exercise test and a physical examination at inclusion and at 3 and 6 months. The 2 groups were similar in terms of ergometric parameters, except for the ischemic threshold, defined as the time to 1-mm ST-segment depression. The latter was shorter in group II. Comparison of exercise tests performed at inclusion and after 6 months of therapy in both groups showed that the ischemic threshold was significantly prolonged (2 minutes 41 seconds; p <0.001 ) in group II. This was not the case for group I, which showed a 41-second prolongation only (difference not significant). The work (kPM) produced at 1-mm ST-segment depression was also significantly increased in group II (1,445.9 kPM; p <0.001) compared with group I (563.7 kPM; p = 0.012). The difference in change between both groups was significant for each variable (respectively, p = 0.008 and p = 0.018). At peak exercise, the duration of effort and total work increased significantly in group II (50 seconds; p = 0.006; 570 kPM, p = 0.004) as opposed to group I (16 seconds, not significant; 221.2 kPM, not significant). The myocardial cost on exercise, expressed as the rate-pressure product/workload at 1-mm ST-segment depression, was significantly decreased in group II (69.9, p <0.001), compared with group I (20.3, not significant). The difference between the 2 groups was significant (p <0.01). This study suggests that combination of diltiazem with trimetazidine in patients with stable angina and positive exercise test, despite diltiazem therapy, may favorably influence the exercise parameters, particularly the ischemic threshold, and lead to a decrease in myocardial cost on exercise. The efficacy of trimetazidine, an antianginal agent with a direct effect on ischemic myocardium, has been tested alone or in combination with β blockers or nifedipine. The combination with diltiazem, a widely used calcium antagonist, has not been studied. The aim of this study was to evaluate the potential benefit of oral trimetazidine (20 mg 3 times daily) in combination with oral diltiazem (60 mg three times daily). This was a multicenter, placebo-controlled study with a follow-up period of 6 months. Patients with stable angina and a positive exercise electrocardiogram before and after 15 days of diltiazem therapy were included. The 67 patients were randomized to diltiazem plus placebo (group I, 35 patients) and diltiazem plus trimetazidine (group II, 32 patients). Follow-up included a bicycle ergometer maximal exercise test and a physical examination at inclusion and at 3 and 6 months. The 2 groups were similar in terms of ergometric parameters, except for the ischemic threshold, defined as the time to 1-mm ST-segment depression. The latter was shorter in group II. Comparison of exercise tests performed at inclusion and after 6 months of therapy in both groups showed that the ischemic threshold was significantly prolonged (2 minutes 41 seconds; p <0.001 ) in group II. This was not the case for group I, which showed a 41-second prolongation only (difference not significant). The work (kPM) produced at 1-mm ST-segment depression was also significantly increased in group II (1,445.9 kPM; p <0.001) compared with group I (563.7 kPM; p = 0.012). The difference in change between both groups was significant for each variable (respectively, p = 0.008 and p = 0.018). At peak exercise, the duration of effort and total work increased significantly in group II (50 seconds; p = 0.006; 570 kPM, p = 0.004) as opposed to group I (16 seconds, not significant; 221.2 kPM, not significant). The myocardial cost on exercise, expressed as the rate-pressure product/workload at 1-mm ST-segment depression, was significantly decreased in group II (69.9, p <0.001), compared with group I (20.3, not significant). The difference between the 2 groups was significant (p <0.01). This study suggests that combination of diltiazem with trimetazidine in patients with stable angina and positive exercise test, despite diltiazem therapy, may favorably influence the exercise parameters, particularly the ischemic threshold, and lead to a decrease in myocardial cost on exercise.