Clinical efficacy of verapamil alone and combined with propranolol in treating patients with chronic stable angina pectoris

To determine the effectiveness of oral verapamil alone and combined with propranolol in patients with chronic angina pectoris, upright bicycle exercise testing was performed in 11 patients in an inpatient single blind crossover study. Compared with placebo, which resulted in an exercise time of 5.1 ± 0.7 minutes (mean ± standard error of the mean), verapamil (480 mg/day) improved exercise time in all patients (mean increment 3.4 ± 0.7 minutes, p <0.001) and was more effective than propranolol (160 to 320 mg/day) (mean increment 1.3 ± 0.6 minutes, p <0.005). Verapamil plus propranolol further increased exercise time (mean increment 4.7 ± 0.7 minutes, p <0.001 versus verapamil alone) and 9 (82 percent) of 11 patients were pain-free during exercise (in contrast to 2 of 11 with propranolol and 1 of 11 with verapamil). Time to 1 mm S-T segment depression was increased by both verapamil (p <0.005) and verapamil plus propranolol (p <0.05) compared with placebo. At the work load causing angina during the placebo study, verapamil decreased heart rate (from 112 ± 3 to 104 ± 3 beats/min, p <0.05) and decreased, but not significantly, pressure-rate product (from 18.3 ± 0.8 × 10³ to 15.9 ± 0.9 × 10³). Verapamil plus propranolol further decreased heart rate (to 76 ± 3, p <0.001) and pressure-rate product (to 9.7 ± 0.5 × 10³, p <0.001). Adverse effects from verapamil, alone or with propranolol, included P-R interval prolongation in most patients, transient atrioventricular nodal Wenckebach block in one patient and exertional dyspnea, orthostatic dizziness or pedal edema in three others. Thus, in this study of patients with stable angina (1) verapamil was a more effective antianginal agent than propranolol, and (2) verapamil plus propranolol provided additional improvement in exercise capacity over either drug alone.