EFFECTS OF THEOPHYLLINE, ATENOLOL AND THEIR COMBINATION ON MYOCARDIAL-ISCHEMIA IN STABLE ANGINA-PECTORIS

The effects of theophylline (400 mg twice a day), atenolol (50 mg twice a day) and their combination on myocardial ischemia were studied in 9 patients with stable angina pectoris in a randomized, single-blind, triple crossover trial. Placebo was administered to the patients during the run-in and the run-off periods. A treadmill exercise test and 24-hour ambulatory electrocardiographic monitoring were obtained at the end of each treatment period. Compared with placebo, theophylline significantly improved the time to onset of myocardial ischemia (1 mm of ST-segment depression) from 7.8 ± 3.7 to 9.5 ± 3.7 minutes (p < 0.03) and the exercise duration from 9 ± 3.4 to 10.1 ± 3.5 minutes (p < 0.04). During atenolol and during combination treatment, the time to the onset of ischemia and the exercise duration were similar (10.8 ± 4.2 and 11.2 ± 3.2 minutes, 11.2 ± 3.6 and 11.5 ± 3.2 minutes, respectively) and longer than during theophylline administration (p < 0.05). Ambulatory electrocardiographic monitoring showed that, during theophylline administration, the heart rate was higher than during placebo throughout the 24 hours (p < 0.05). During atenolol and during combination treatment the heart rate was similar and in both cases lower than during placebo (p < 0.05). Compared with placebo, theophylline decreased the total ischemic time from 97 ± 110 to 70 ± 103 minutes (p < 0.05). During combination treatment the total ischemic time (5.6 ± 8.5 minutes) was not statistically different from that during atenolol administration (18 ± 29 minutes), although it was significantly lower than that observed during theophylline administration (p < 0.05). Thus, in patients with stable angina pectoris the long-term administration of theophylline improves myocardial ischemia, but to a lesser degree than atenolol. Despite the fact that atenolol abolishes the undesirable chronotropic effect of theophylline and the latter probably reduces the undesirable increase of cardiac volumes caused by atenolol, their combination does not show detectable additive effects. © 1990.