PREVENTION / 3-ADRENERGIC BLOCKADE Abrupt withdrawal of lP-blockade therapy in patients with myocardial infarction : effects on infarct size , left ventricular function , and hospital course *

The effects of abrupt withdrawal or continuation of fl-blockade therapy during acute myocardial infarction were evaluated in 326 patients participating in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). Thirty-nine patients previously receiving a f8-blocker and randomly selected for withdrawal of fl-blockers and placebo treatment during infarction (group 1) were compared with 272 patients previously untreated with fl-blockers who were also randomly assigned to placebo therapy (group 2). There were no significant differences between the two groups in MB creatine kinase isoenzyme (15.8 10.9 vs 18.2 + 14.4 g-eq/m2, respectively) estimates of infarct size, radionuclide-determined left ventricular ejection fractions within 18 hr of infarction (0.44 0.15 vs 0.47 0.16) or 10 days later (0.42 0.14 vs 0.47 0.16), creatine kinase-determined incidence of infarct extension (13% vs 6%), congestive heart failure (43% vs 37%), nonfatal ventricular fibrillation (5% vs 7%), or in-hospital mortality (13% vs 9%). Patients in group 1 had more recurrent ischemic chest pain (p = .002) within the first 24 hr after infarction, but not thereafter. However, this did not appear to be related to a rebound increase in systolic blood pressure, heart rate, or double product. In a separate analysis, 20 propranolol-eligible group 1 patients randomly selected for withdrawal of fl-blockade (group 3) were compared with 15 patients randomly selected for continuation of prior fiblockade therapy (group 4). This comparison yielded similar results. These data indicate that the ,f-blockade withdrawal phenomenon is not a major clinical problem in patients with acute myocardial infarction. f-Blockade therapy can be discontinued abruptly during acute myocardial infarction if clinically indicated. Circulation 73, No. 6, 1281-1290, 1986. From the Department of Internal Medicine (Cardiology Division) of the University of Texas Health Science Center, Dallas, and the MILIS Clinical Units at Barnes Hospital, St. Louis, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Medical Center Hospital of Vermont, Burlington, and Parkland Memorial Hospital, Dallas. The research on which this publication is based was performed by the Multicenter Investigation of the Limitation of Infarct Size (MILIS) Group pursuant to contract numbers NO 1 -HV-7-2940, 7-2941, 7-2942, and 7-2979 with the National Heart, Lung, and Blood Institute, National Institutes of Health, U. S. Department of Health and Human Services. Address for correspondence: James T. Willerson, M.D., Cardiology Division, University of Texas Health Science Center, 5323 Harry Hines Blvd., Dallas, TX 75235. Received Aug. 6, 1985; revision accepted March 20, 1986. *All editorial decisions for this article, including selection of reviewers and the final disposition, were made by a guest editor. This procedure applies to all manuscripts with authors from the Washington University School of Medicine. Vol. 73, No. 6, June 1986 THERE IS CURRENT widespread concern that the sudden withdrawal of f-adrenoreceptor-blocking agents from patients with ischemic heart disease may result in a rebound adrenergic hypersensitivity manifested by an exacerbation of angina pectoris,'-5 ventricular arrhythmias, 3, 6,7 myocardial infarction,24 or sudden death.2M Several mechanisms have been proposed to account for these phenomena, including platelet hyperaggregability,t5 increased plasma renin activity,4 8an unfavorable leftward shift in the oxyhemoglobin dissociation curve,4'9 an increase in triiodothyronine levels,'0 a reactive increase in plasma catecholamines,11 increased numbers of fi-adrenergic