EFFECTS OF BETA-BLOCKADE ON SUDDEN CARDIAC DEATH DURING ACUTE MYOCARDIAL-INFARCTION AND THE POSTINFARCTION PERIOD

About half of all deaths after myocardial infarction (MI) are sudden c ardiac deaths. Most of these are thought to be due to ventricular fibr illation (VF). A number of interventions and many different antiarrhyt hmic agents have been investigated, but so far only beta-blocker thera py has been found to produce significant reductions in the risk of sud den cardiac death after MI. Reductions in total mortality and sudden c ardiac death were first reported in 1981 in 3 placebo-controlled studi es, the Norwegian Timolol Study, the American Beta-Blocker Heart Attac k Trial (BHAT), and the Goteborg Metoprolol Trial. A few years later, two very large trials, the Metoprolol in Acute Myocardial Infarction ( MIAMI) study and the First International Study of Infarct Survival (IS IS-1), which included 6,000 and 16,000 patients, respectively, showed that beta-blocker therapy could reduce mortality within the first 2 we eks after onset of MI. Data from 24 postinfarction studies with long-t erm follow-vp show an average 20% mortality reduction over 2 years. Po oled results of 28 short-term, randomized, placebo-controlled trials i n which beta blockers were given intravenously shortly after onset of MI indicate an average 13% mortality reduction within 2 weeks. In the 16 studies in which the sudden cardiac death rate was reported, the be neficial effect of beta blockade was even more marked: a 34% average r eduction of risk. Not all studies with beta blockers, however, have de monstrated a significant reduction in the incidence of sudden cardiac death. Such an effect has been clearly demonstrated only for the more lipophilic beta blockers (timolol, metoprolol, and propranolol). Two o f these lipophilic beta blockers, metoprolol and propranolol, have als o been shown to prevent VF after MI in clinical studies. Based on obse rvations from animal experiments, it has been proposed that beta block ers with a high degree of lipophilicity penetrate the brain and thereb y maintain high vagal tone during stress, A combination of direct anti -ischemic effects due to beta(1) blockade and preservation of vagal to ne appears to prevent VF in these animal models. Further clinical stud ies are needed to explore this hypothesis. (C) 1997 by Excerpta Medica , Inc.