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Perioperative myocardial ischemia occurs in 20–40% of patients at risk for cardiac complications and is associated with a ninefold increase in risk for perioperative cardiac death, myocardial infarction, or unstable angina, and a twofold long-term risk. Perioperative atenolol administration reduces the risk of death for as long as 2 yr after surgery. This randomized, placebo-controlled, double-blinded trial tested the hypothesis that perioperative atenolol administration reduces the incidence and severity of perioperative myocardial ischemia, potentially explaining the observed reduction in the risk for death.Two-hundred patients with, or at risk for, coronary artery disease were randomized to two study groups (atenolol and placebo). Monitoring included a preoperative history and physical examination and daily assessment of any adverse events. Twelve-lead electrocardiography (ECG), three-lead Holter ECG, and creatinine phosphokinase with myocardial banding (CPK with MB) data were collected 24 h before until 7 days after surgery. Atenolol (0, 5, or 10 mg) or placebo was administered intravenously before induction of anesthesia and every 12 h after operation until the patient could take oral medications. Atenolol (0, 50, or 100 mg) was administered orally once a day as specified by blood pressure and heart rate.During the postoperative period, the incidence of myocardial ischemia was significantly reduced in the atenolol group: days 0–2 (atenolol, 17 of 99 patients; placebo, 34 of 101 patients; P = 0.008) and days 0–7 (atenolol, 24 of 99 patients; placebo, 39 of 101 patients; P = 0.029). Patients with episodes of myocardial ischemia were more likely to die in the next 2 yr (P = 0.025).Perioperative administration of atenolol for 1 week to patients at high risk for coronary artery disease significantly reduces the incidence of postoperative myocardial ischemia. Reductions in perioperative myocardial ischemia are associated with reductions in the risk for death at 2 yr.