DISCORDANCE BETWEEN EFFECTS OF ANTIISCHEMIC THERAPY ON AMBULATORY ISCHEMIA, EXERCISE PERFORMANCE AND ANGINAL SYMPTOMS IN PATIENTS WITH STABLE ANGINA-PECTORIS

Objectives. We sought to define the extent to which the therapeutic ef ficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically e xercise test performance and anginal symptoms. Background. Some studie s have shown that the presence and severity of ambulatory ischemia are predictive of anginal symptoms and exercise test performance, whereas other studies have not. Less is known about effects of antianginal tr eatment and whether response to therapy for one clinical manifestation reflects therapeutic responses for other clinical manifestations. Met hods. We studied 50 patients in the Angina and Silent Ischemia Study w ho had documented coronary disease, an exercise test positive for isch emia, the presence of ambulatory and asymptomatic ischemia on ambulato ry electrocardiographic (ECG) Holter monitoring and stable anginal sym ptoms. Patients received maximally tolerated doses of sustained releas e propranolol (mean 293 mg/day), sustained release diltiazem (mean 350 mg/day), nifedipine (mean 79 mg/day) and placebo, each for 2-week per iods in a double-blind, crossover fashion. Patients' responses to trea tment were assessed by 48-h ambulatory ECG monitoring, exercise test ( standard Bruce protocol) and diaries of angina. Levels of efficacy for each agent and for each clinical measure were compared using Spearman correlation analysis. Results. With placebo there was no correlation among the frequency of ischemic episodes by ambulatory ECG monitoring, exercise time to 1.0-mm ST segment depression or frequency of anginal episodes. Furthermore, for a given patient the efficacy of each activ e medication in reducing ambulatory ischemia was not correlated with r esponse in anginal symptoms or exercise test performance (r = -0.21 to 0.24, p = NS). Within each of these clinical measures, efficacy of on e drug was more strongly correlated with efficacy of another drug (r = 0.64 to 0.81 for ambulatory ischemia, 0.48 to 0.56 for exercise test performance and 0.16 to 0.54 for anginal symptoms). Conclusions. Diffe rent measures of ischemia, specifically ambulatory ischemia assessed b y ambulatory ECG monitoring, exercise performance on exercise test and anginal symptoms, are independent. Efficacy for each clinical end poi nt must be assessed separately when considering response to drug treat ment.