Mechanisms for the early mortality reduction produced by beta-blockade started early in acute myocardial infarction: ISIS-1. ISIS-1 (First International Study of Infarct Survival) Collaborative Group

Abstract

In a large randomised trial of early beta-blockade in acute myocardial infarction (ISIS-1), almost all the reduction in mortality associated with the use of atenolol occurred on the day of admission or on the subsequent day. To help determine the mechanisms that might be responsible for this retrospective observation, case notes were obtained for British, Irish, and Scandinavian patients who died during this early period. Of 217 early deaths adequate records were available for 193 (79 allocated atenolol and 114 allocated control). In the atenolol group, necropsy had shown cardiac rupture in 5 patients, and a further 15 in whom necropsy had not been done had had electro-mechanical dissociation (total, 20 early deaths from these causes); among control patients the corresponding numbers were 17 and 37 (total, 54 such deaths). Electro-mechanical dissociation was probably a manifestation of acute rupture, and the observed difference in the numbers with this complication was responsible for much of the difference in early mortality. There was a slightly higher incidence of fatal ventricular fibrillation and aortic dissection in the control group, and of bradycardia/asystole in the atenolol group. The data did not indicate any substantial contribution from mechanisms such as limitation of infarct size or prevention of reinfarction or cardiac arrest.