Diltiazem dose responses in sustained therapy for stable angina pectoris.

Fifteen patients with stable effort angina were treated for 2 weeks with each of diltiazem 120 mg, 240 mg, 360 mg or placebo in a double-blind crossover protocol. The frequency of angina was decreased from 7.2 +/- 1.1 (mean +/- S.D.) episodes per 2 weeks with placebo to 5.9 +/- 5.2 (N.S.), 4.1 +/- 1.1 (p less than 0.01) and 1.5 +/- 0.8 (p less than 0.005) with 120 mg, 240 mg and 360 mg diltiazem respectively. Similar decreases occurred in nitroglycerin consumption. Ten hours after the last dose of each treatment period, each patient was challenged with 120 mg diltiazem. Treadmill exercise testing was carried out at 0, 1, 2, 4 and 8 hours. Time to onset of angina and 0.1m V ST depression increased at 1 hour, was maximal at 2 and 4 hours, and remained elevated at 8 hours. Two weeks of sustained treatment with diltiazem did not alter the responses in treadmill performance to 120 mg diltiazem. Hemodynamic changes were consistent with decreased myocardial oxygen demand and increased myocardial oxygen supply by diltiazem. There was no significant attenuation of hemodynamic response with sustained therapy. Trough plasma levels of diltiazem at 10 hours following the last dose of sustained therapy varied in a dose-dependent manner. However, corresponding exercise tolerances were identical regardless of the plasma level. Peak drug levels at 4 hours following 120 mg aldo did not correlate with exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)