Efficacy of diltiazem in angina on effort: a multicenter trial

During a multicenter study 57 patients with exercise-induced angina were evaluated with serial exercise testing to assess the efficacy of diltiazem, a calcium slow channel blocking agent, compared with a placebo. The study consisted of a 1 week single-blind placebo stabilization period followed by a double-blind triple crossover between diltiazem and placebo. Three dose levels were tested (120, 180 and 240 mg/day) in each patient. For the three time-related variables there was a significant dose-related response, with 240 mg/day being the most effective. The increases, over the washout placebo stabilization values, of the time-related variables for the 240 mg/day week compared with the corresponding placebo week were total duration of exercise 1.87 versus 1.05 minutes (p less than 0.002), time to onset of angina 1.81 versus 1.17 minutes (p less than 0.01) and time to appearance of 1 mm S-T segment depression 1.81 versus 1.01 minutes (p less than 0.002). Analysis of exercise variables indicated a significant reduction in heart rate, diastolic blood pressure, and pressure-rate product at submaximal exercise after administration of diltiazem. Diastolic blood pressure was significantly reduced at maximal exercise. Heart rate and pressure-rate product were unchanged at rest during submaximal or maximal exercise. Submaximal and maximal exercise S-T depression was not significantly altered by diltiazem. The reduction in pressure-rate product at submaximal exercise was a possible mechanism for the drug's beneficial effect in enhancing the three time-related variables.