Ambulatory Patients With Coronary Artery Disease

Ambulatory electrocardiographic (ECG) monitoring of patients with chronic stable angina has demonstrated frequent and prolonged episodes of ischemic ST segment depression, but its clinical use requires an understanding of the components and extent of variability. Therefore, variations in the frequency and duration of episodes of ST segment depression were evaluated with ambulatory ECG recording at daily, weekly, and monthly intervals in 42 patients with chronic stable angina and known coronary artery disease. Data were analyzed with a nested analysis of variance design that yields estimates of variance components. From the estimates of variance components, power calculations and minimum significant percent reductions in frequency and duration of ischemia were derived. During 4,656 hours of ambulatory ECG monitoring, 1,262 episodes of ischemic ST segment depression were detected. The frequency of episodes was 6.3 ± 0.45/24 hr (mean ± SEM), and the duration of episodes was 18.3 ± 2.8/24 hr. Because of variability over time, the ability to detect significant changes was dependent upon the number of subjects, length of monitoring period, and intervals between monitoring periods. In a clinical trial, for example, a sample size of 25 patients monitored for 48 hours with 1 week between control and test conditions would require a 65% reduction in frequency, whereas a sample size of 50 patients monitored under similar conditions would require a 46% reduction in frequency, to attribute the change with 90% power to a therapeutic intervention rather than to a spontaneous variation. When monitoring a single patient for 48 hours with 1 week or 1 month between control and repeat monitoring sessions, episodes of ischemic ST depression must be eliminated to detect significant therapeutic changes in ischemic activity at the 95% confidence level. Therefore, an understanding of the variability of episodes of ischemic ST segment depression on ambulatory ECG monitoring permits the rational design of clinical trials and individual assessment in patients with active ischemic heart disease. (Circulation 1988;78:60-67)