Variability of episodic ST segment depression in chronic stable angina: implications for individual and group trials of therapeutic efficacy.

OBJECTIVES: This study was conducted to quantify the variability of episodic ST segment depression in chronic stable angina and enable assessment of the impact of interventions in individual patients and clinical trials.
BACKGROUND: Episodic myocardial ischemia can be detected by ST segment depression on ambulatory electrocardiographic (ECG) monitoring and may be important for the assessment of outcome. Variability of the number and duration of episodes has important implications for monitoring and therapeutic strategies.
METHODS: We studied 36 patients, aged 37 to 77 years (median 60), with stable angina and coronary artery disease by serial ambulatory ECG monitoring for a total of 415 days. A nested analysis of variance was carried out to assess the sources of spontaneous variation, and power function analyses were performed.
RESULTS: During 415 days of monitoring, 1,882 episodes of ST segment depression were detected (mean frequency +/- SD, 4.5 +/- 4.1/day, duration 67 +/- 87 min/day, 25% in association with pain). Considerable variability was found within and between patients for both the number and the duration of ischemic episodes. For a patient monitored for 24 h before and after treatment, an 81% reduction in the number of episodes would be required to show a significant benefit; if monitoring were performed for 4 days four times before and after therapy, a 46% decrease would be significant. In clinical trials, a true reduction of > or = 15% in ischemic episodes is required to have sufficient power to obtain statistical significance.
CONCLUSIONS: The natural variability of transient myocardial ischemia in patients with chronic stable angina can be quantified and this information used to study the effectiveness of interventions in both individual patients and clinical trials.