Differences in response to single dose and steady-state therapy with verapamil in stable angina

Ten patients with stable effort angina were studied in a randomized double-blind and placebo-controlled trial to compare the antianginal efficacy of "acute" and "chronic" (after reaching a steady-state level) treatment with verapamil. Efficacy was assessed by exercise testing after a 120 mg single-dose and at the end of a seven-dose course of 120 mg of verapamil given thrice daily. Three daily exercise tests were performed the first, second and fifth day of the study protocol at 8, 12 and 16 hours. Eight hours after the last dose was given, exercise time increased by 54 +/- 30 sec after a single-dose of verapamil and by 156 +/- 31 sec after seven-doses of verapamil (P less than 0.05 as compared to single-dose verapamil). The time to 1 mm depression of the ST segment increased by 30 +/- 20 sec after a single-dose of verapamil and by 66 +/- 28 sec after seven-doses of verapamil (P less than 0.01 as compared to single dose verapamil). Six of the ten patients became free from angina on treadmill exercise after a seven-dose course of verapamil, but only one patient became free from angina after acute testing with a single-dose of verapamil. It is concluded that several doses of verapamil are required to achieve an optimal anti-ischemic effect, as suggested by the pharmacodynamic properties of this drug. Once steady-state is achieved, the effects of verapamil remain for at least 8 hours, so that an administration schedule of three times daily protects the patient for a 24-hour period.