EFFECTS OF TREATMENT ON OUTCOME IN MILDLY SYMPTOMATIC PATIENTS WITH ISCHEMIA DURING DAILY-LIFE - THE ATENOLOL SILENT ISCHEMIA STUDY (ASIST)

Background Detection of asymptomatic ischemia in patients with coronar y artery disease has been associated with increased risk for adverse o utcome, but treatment of patients with asymptomatic ischemia remains c ontroversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ische mia. Methods and Results A multicenter, randomized, double-blind, plac ebo-controlled study of asymptomatic or minimally symptomatic outpatie nts with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 y ear by Kaplan-Meier analysis. Events were death, resuscitated ventricu lar tachycardia/fibrillation, myocardial infarction, hospitalization f or unstable angina, aggravation of angina, or revascularization. The s econdary outcome was ischemia during ambulatory ECG monitoring at 4 we eks. Three hundred six outpatients with mild or no angina (Canadian Ca rdiovascular Society class I or II), abnormal exercise tests, and isch emia on ambulatory monitoring were randomized to receive either atenol ol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/-SD, 3.6+/-4.2 versus 1.7+/-4.6 episodes, P<.001) and average durati on (30+/-3.3 versus 16.4+/-6.7 minutes, P<.001) of ischemic episodes p er 48 hours of ambulatory monitoring decreased in atenolol- compared w ith placebo-assigned patients (4.4+/-4.6 to 3.1+/-6.0 episodes and 36. 6+/-4.1 to 30+/-5.5 minutes). Event-free survival improved in atenolol -treated patients (P<.0066), who had an increased time to onset of fir st adverse event (120 versus 79 days) and fewer total first events com pared with placebo (relative risk, 0.44; 95% confidence intervals, 0.2 6 to 0.75; P=.001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillatio n, nonfatal myocardial infarction, or hospitalization for unstable ang ina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P=.175). The most powerful univariate and mu ltivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generall y similar comparing atenolol- and placebo-treated patients, although b radycardia was more frequent with atenolol. Conclusions Atenolol treat ment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients co mpared with placebo.