Long-term effects of the alpha, beta-blocker arotinolol on stable effort angina pectoris using 24-hour ambulatory electrocardiographic monitoring: an open-label, pilot study

Abstract

Background: Beta-blockers are effective in patients with effort angina pectoris. However, there have been no previous reports on the long-term effects of beta-blocker therapy using ambulatory electrocardiographic (AECG) monitoring according to a MEDLINE ® search. Objective: This study was undertaken to assess the long-term effects of the alpha, beta-blocker arotinolol in patients with stable effort angina pectoris using AECG monitoring. Methods: This pilot study involved patients with Canadian Cardiovascular Society class I or II stable effort angina pectoris and left ventricular ejection fraction >40% assessed using 2-dimensional echocardiography in whom percutaneous transluminal coronary angioplasty and coronary artery bypass grafting had not been performed. Patients were excluded if they were >75 years of age, had congestive heart failure of New York Heart Association class III or IV, or had a confirmed diagnosis of an illness likely to shorten their life span (eg, cancer, cirrhosis). Effort angina pectoris was diagnosed based on chest pain on effort and myocardial ischemia as demonstrated by stress thallium-201 myocardial perfusion scintigraphy and significant ST-segment depression on exercise electrocardiogram. The alpha, beta-blocker arotinolol 20 mg/d, divided into 2 doses of 10 mg each, was administered orally for 2 years. Patients were seen by the same physician at 2-week intervals during the first 6 weeks of treatment and at 4-week intervals thereafter, at which times chest pain, nitrate consumption, blood pressure, and heart rate were assessed. AECG monitoring was performed before treatment, at 6 weeks, and after 2 years of treatment. Results: Results were assessable in 12 of 18 patients at 4 institutions (6 withdrew from the study within 4 weeks of treatment) with a mean (±SD) age of 65 ± 3 years. The number of episodes per day of chest pain decreased significantly ( P < 0.05) at 6 weeks and became rare 2 years after treatment. There was significant improvement ( P < 0.05) during the daytime at both 6 weeks and 2 years in the number of episodes (0.1 ± 0.4 and 0.1 ± 0.3, respectively, vs 0.9 ± 1.1) and the duration (3.8 ± 7.0 and 0.4 ± 1.6 minutes, respectively, vs 40.9 ± 27.8 minutes) of ST-segment depression. The incidence and duration of ST-segment depression decreased significantly ( P < 0.05) in the nighttime at 2 years compared with baseline (0.2 ± 0.04 and 0.04 ± 1.6 minutes vs 1.9 ± 0.9 and 23.9 ± 31.5 minutes, respectively). Daytime heart rate decreased significantly ( P < 0.05), from 84 ± 11 beats/min before treatment to 69 ± 12 beats/min at 6 weeks and 67 ± 12 beats/min at 2 years; nighttime heart rate also decreased significantly ( P < 0.05), from 70 ± 11 beats/min before treatment to 65 ± 9 beats/min at 6 weeks and 59 ± 7 beats/min at 2 years. Conclusions: Arotinolol improved the incidence and duration of ST-segment depression in patients with stable effort angina pectoris on AECG monitoring by decreasing heart rate. Because the improvement was more marked after 2 years than after 6 weeks, we concluded that arotinolol is beneficial in the long-term treatment of patients with stable effort angina pectoris, although a larger study using a control group is needed to confirm our results.