The antianginal efficacy of bepridil, a calcium antagonist with an extended plasma elimination half-life, has been compared with placebo and the calcium antagonists nifedipine and diltiazem in patients refractory to diltiazem. The earliest observations in the United States of antianginal effects of bepridil were revealed in a single-blind, multicenter, placebo-controlled trial of 77 patients with chronic stable angina pectoris that demonstrated that bepridil (300 mg/day) improved exercise duration by 26%, from 6.9 +/- 0.4 (standard error of the mean) to 8.7 +/- 0.5 minutes (p less than 0.001), and exercise work by 52%, from 2.7 +/- 0.3 to 4.1 +/- 0.4 x 10(-3) KPM (p less than 0.001), on a standardized treadmill protocol, and it reduced angina frequency by 68%, from 8.5 +/- 1.1 to 2.7 +/- 0.7 attacks per week, and nitroglycerin use by 76% (p less than 0.001). Minor side effects such as nausea, epigastric discomfort, and tremor were infrequent and no major side effects occurred. Double-blind, parallel-design treatment evaluations confirmed beneficial effects of bepridil alone and in combination with beta blockade. Chronic efficacy was confirmed by evaluations up to 24 months in a controlled withdrawal study. Antianginal effects of nifedipine were compared with those of bepridil in a double-blind, parallel group study of 101 patients with chronic stable angina treated for 3 months. Bepridil (mean final dose 284 mg/day; range 200-400 mg/day) produced modest but statistically significantly (p less than 0.05) greater improvements in exercise work, time to angina, or 1 mm ST-segment change than nifedipine (mean final dose 59 mg/day; range 30-120 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)