TRIMETAZIDINE EUROPEAN MULTICENTER STUDY VERSUS PROPRANOLOL IN STABLEANGINA-PECTORIS - CONTRIBUTION OF HOLTER ELECTROCARDIOGRAPHIC AMBULATORY MONITORING

The major objective of the Trimetazidine European Multicenter Study (T EMS) was to compare in a double-blind trial the anti-ischemic effects of trimetazidine (20 mg 3 times daily) with those of propranolol (40 m g 3 times daily). The inclusion criteria were; based on an abnormal re sponse to a multistage exercise test. After 3 months of treatment the improvements noted in all exercise testing data were similar in the tr imetazidine and propranalol groups; similar data were obtained for the grades and severity of anginal attacks during daily life (from patien t diaries). A 24-hour Holter monitoring was performed at entry and at the end of the study, but an abnormal Holter monitoring (1-mm ST-segme nt depression during at least 1 minute) was not an inclusion criterion . This explains why at entry only 50% of the patients in both groups h ad an abnormal Holter recording. After 3 months of treatment, there we re no significant differences between the 2 groups, but we observed ct trend toward a decrease in ambulatory ischemia in the trimetazidine g roup and a trend toward an increase in ambulatory ischemia in the prop ranolol group. These data in the propranolol group are in total disagr eement with the available literature on beta blockers, which was due t o a totally erratic behavior pattern in 2 patients in the propranalol group. When we excluded these 2 erratic cases from the propranolol gro up and extended our analysis to all available paired comparisons (day -14 to day 30 and day 0 to day 90), we were able to compare 44 and 60 observations, both off therapy and an either propranolol or trimetazid ine, respectively. The number of ischemic episodes was significantly r educed with trimetazidine (p <0.02) but not with propranolol. The tota l duration of ischemia was reduced (but not significantly) ih the trim etazidine group; surprisingly, this reduction was essentially due to a reduction in symptomatic ischemic episodes. A circadian ischemic prof ile was noted in both groups, brit it was notably more reduced in the trimetazidine group; surprisingly, this reduction was also essentially due to a reduction in symptomatic ischemic episodes. We conclude from these data that, (I)to draw conclusions on ischemic Holter monitoring data, an abnormal ischemic Hotter should be one of the criteria to en ter the study; (2) a 48-hour ambulatory recording is likely to provide more reliable information; and (3) much larger groups should be studi ed to avoid statistical interference from erratic cases.