EFFECT OF DILTIAZEM ON SYMPTOMATIC AND ASYMPTOMATIC EPISODES OF ST SEGMENT DEPRESSION OCCURRING DURING DAILY LIFE AND DURING EXERCISE

Background. Silent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear. Methods and Results. Sixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p = 0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 +/- 148 from 296 +/- 154 seconds (p = 0.005). Although less frequent with diltiazem administration (45 versus 54 patients, p < 0.03), exercise-induced ST depression was more often asymptomatic (98% versus 72% of patients, p < 0.0001). Conclusions. Diltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease.