• A Hjalmarson.
• Institute of Heart and Lung Diseases, Sahlgrenska University Hospital, Göteborg, Sweden.
• Am. J. Cardiol. 1997 Nov 13;80(9B):35J-39J.

AbstractAbout half of all deaths after myocardial infarction (MI) are sudden cardiac deaths. Most of these are thought to be due to ventricular fibrillation (VF). A number of interventions and many different antiarrhythmic agents have been investigated, but so far only beta-blocker therapy has been found to produce significant reductions in the risk of sudden cardiac death after MI. Reductions in total mortality and sudden cardiac death were first reported in 1981 in 3 placebo-controlled studies, the Norwegian Timolol Study, the American Beta-Blocker Heart Attack Trial (BHAT), and the Göteborg 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 (ISIS-1), which included 6,000 and 16,000 patients, respectively, showed that beta-blocker therapy could reduce mortality within the first 2 weeks after onset of MI. Data from 24 postinfarction studies with long-term follow-up show an average 20% mortality reduction over 2 years. Pooled results of 28 short-term, randomized, placebo-controlled trials in 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 beneficial effect of beta blockade was even more marked: a 34% average reduction of risk. Not all studies with beta blockers, however, have demonstrated 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 of these lipophilic beta blockers, metoprolol and propranolol, have also been shown to prevent VF after MI in clinical studies. Based on observations from animal experiments, it has been proposed that beta blockers with a high degree of lipophilicity penetrate the brain and thereby maintain high vagal tone during stress. A combination of direct anti-ischemic effects due to beta1 blockade and preservation of vagal tone appears to prevent VF in these animal models. Further clinical studies are needed to explore this hypothesis.

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