Effects of lisinopril, atenolol, and isosorbide 5-mononitrate on angina pectoris and QT dispersion in patients with syndrome X: An open-label, randomized, crossover study

Abstract

Background: The triad of angina pectoris, a positive exercise electrocardiographic test, and a normal coronary angiogram is described as syndrome X. Because the definite underlying pathophysiologic mechanism of syndrome X is not fully understood, there is no consensus about its treatment. It has been suggested that the prolonged QT interval observed in patients with syndrome X is due to autonomic nervous system dysfunction. Objective: The purpose of this study was to investigate the effects of treatment with lisinopril, atenolol, and isosorbide 5-mononitrate on angina pectoris and QT dispersion in patients with syndrome X. Methods: Adult patients with syndrome X and a control group of healthy subjects were included in this open-label, crossover study. After a 30-day washout period, patients with syndrome X were randomized into 3 different groups and were sequentially given, in a crossover study design, the angiotensin-converting enzyme inhibitor lisinopril (10 mg/d), the beta-blocker atenolol (50 mg/d), and isosorbide 5-mononitrate (60 mg/d) for 30 days each. Treatment periods were separated by a 10-day washout period. At the end of each 30-day period, QT dispersion (defined as maximal QT interval minus minimal QT interval) was measured on 12-lead electrocardiography, and patients' diary records were assessed to calculate the number of angina attacks and use of sublingual nitrates. Only an electrocardiographic analysis for QT dispersion was performed for the control group; no medication was given. This group was included in our study to test the validity of our method of determining QT dispersion. Results: A total of 21 patients (18 women and 3 men; mean age, 49.5 ± 10.4 years) and 18 control subjects (13 women and 5 men; mean age, 47.6 ± 9.8 years) were enrolled in the study. QT dispersion was found to be significantly increased in patients with syndrome X compared with the control group (102.0 ± 50.9 milliseconds vs 38.9 ± 18.5 milliseconds, P < 0.01). QT dispersions were 103.2 ± 42.1 milliseconds, 72.4 ± 35.0 milliseconds, and 80.7 ± 25.4 milliseconds after treatment with lisinopril, atenolol, and isosorbide 5-mononitrate, respectively. QT dispersion was reduced significantly versus baseline only after treatment with atenolol. The number of anginal episodes and sublingual nitrate consumption decreased significantly during the atenolol and lisinopril treatment periods. Conclusions: Our data suggest that increased sympathetic activation may be the underlying pathophysiologic mechanism of syndrome X and that atenolol appeared to be more effective than lisinopril or isosorbide 5-mononitrate for its treatment.