Dose response effects of diltiazem on treadmill tolerance in chronic stable angina: a randomized double-blind, placebo-controlled crossover trial.

Sixteen patients with stable angina underwent treadmill exercise on 4 separate days prior to and at 1, 2, 4 and 8 hours following a single dose of 30 mg, 60 mg or 90 mg of diltiazem or identical placebo. Prolongation of exercise time to the onset of angina, 0.1 mV ST depression and to maximal exercise developed within 2 hours, peaked at 4 hours and persisted for 8 hours. Time to angina at control with placebo and 90 mg of diltiazem was 399 +/- 176 and 368 +/- 193 seconds respectively (X +/- SD) and 4 hours post drug was 474 +/- 216 and 635 +/- 209 seconds respectively (p less than 0.001). The pressure-rate product at angina 4 hours following 90 mg of drug was higher than after placebo (189 +/- 48 and 168 +/- 44 mmHg-1 X 10(-2) respectively). Heart rate increased (127 +/- 24 vs. 117 +/- 19 bpm) while systolic pressure was unchanged (147 +/- 17 and 142 +/- 21 mmHg). During submaximal exercise at a fixed work load, diltiazem, 90 mg, decreased heart rate from 114 +/- 14 to 97 +/- 18 bpm (p less than 0.005), systolic blood pressure from 148 +/- 19 to 135 +/- 18 mmHg (p less than 0.005) and rate-pressure product from 169 +/- 37 to 131 +/- 36 mmHg-1 X 10(-2) (p less than 0.005). Peak diltiazem plasma levels occurred at 4 hours, being 37 +/- 34, 74 +/- 67 and 106 +/- 68 ng/ml for 30, 60 and 90 mg respectively. Drug levels paralleled increased exercise tolerance when mean data were considered; however, correlation on an individual basis was poor.(ABSTRACT TRUNCATED AT 250 WORDS)