Cardioprotection with beta-adrenoceptor blockers. Does lipophilicity matter?

Abstract

Beta-blockers have several beneficial cardiovascular effects in patients with hypertension, angina pectoris, myocardial infarction, and congestive heart failure. In patients with myocardial infarction and congestive heart failure some beta-blockers have been found to reduce mortality and morbidity. The beta-blockers with a proven effect on prognosis include timolol, metoprolol, propranolol, bisoprolol, and carvedilol.

One important question is whether all cardiovascular effects obtained by beta-blockers can be considered to be class effects. The beta-blockers with favorable effects on prognosis include two with more selective beta₁-receptor blockade (metoprolol and bisoprolol) and three non-selective (timolol, propranolol and carvedilol). One non-selective beta-blocker, which also has a more pronounced class III effect, sotalol, has been studied in a large postinfarction study without a significant effect on mortality. However, sotalol reduced the incidence of reinfarction similarly to the other beta-blockers with proven effect on mortality after myocardial infarction. Sotalol had no influence at all on sudden cardiac death, while all the other beta-blockers referred to above have a very marked effect on sudden cardiac death, in fact more marked than on overall mortality. The beta-blockers with proven effect on mortality and on sudden death have one property in common and that is some degree of lipophilicity. Sotalol and atenolol are hydrophilic. From animal experimental data it has been suggested that beta-blockers with some degree of lipophilicity penetrate into the brain and have an indirect effect on vagal activity, which is of importance for prevention of ventricular fibrillation and sudden cardiac death.

It can be summarized that some beta-blockers have been found to reduce mortality and sudden cardiac death in patients after myocardial infarction and in congestive heart failure, while others have not. It seems that the major properties of the beta-blockers with proven effects on mortality and sudden cardiac death are beta₁-receptor blockade and some degree of lipophilicity. Until we know more about the mechanisms behind prevention of death and especially sudden cardiac death by beta-blockers, only drugs with proven effects on prognosis should be used.