beta-Adrenoceptor antagonists (beta-blockers) provide multiple benefits to patients with
coronary artery disease. The 2001 American Heart Association and American College of Cardiology (AHA/ACC) guidelines for
secondary prevention of
myocardial infarction (MI) recommend initiating beta-
adrenoceptor blockade in all post-MI patients and continuing
therapy indefinitely.
Atenolol and
metoprolol have been shown to decrease vascular mortality in the acute-MI period. In the post-MI period
timolol provided a 39% reduction in mortality in the Norwegian Multicenter Study group and
propranolol was associated with a 26% reduction in mortality in BHAT (Beta-blocker
Heart Attack Trial).
beta-Adrenoceptor antagonist therapy results in reduction of myocardial
oxygen demand and is therefore also effective for the treatment of
angina pectoris. In CAST (
Cardiac Arrhythmia Suppression Trial)
beta-adrenoceptor antagonist therapy was associated with a significant reduction in arrhythmic death or
cardiac arrest. In the post-MI
amiodarone trials EMIAT (European
Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian
Amiodarone Myocardial Infarction Trial) there was a mortality benefit and decreased arrhythmic death in patients who received both
amiodarone and
beta-adrenoceptor antagonist therapy, compared with patients receiving
amiodarone therapy alone. In the post-MI
defibrillator (implantable cardioverter defibrillator [ICD]) trials, AVID (Antiarrhythmic Versus
Implantable Defibrillator) and MUSTT (Multicenter Unsustained
Tachycardia Trial),
beta-adrenoceptor antagonist therapy was independently associated with improved overall survival. The exception was the ICD patients in MUSTT, and the benefit was attenuated in the
amiodarone and ICD patients in AVID.AHA/ACC guidelines recommend the use of
beta-adrenoceptor antagonists in all patients with symptomatic
left ventricular dysfunction, based on several large, controlled
heart failure trials. Extended-release
metoprolol succinate reduced all-cause mortality by 34% in MERIT-HF (
Metoprolol Controlled-Release/Extended-Release Randomized Intervention Trial in
Heart Failure).
Bisoprolol was associated with a 34% mortality benefit in CIBIS-II (Cardiac Insufficiency
Bisoprolol Study II) and
carvedilol was associated with a 35% mortality reduction in the COPERNICUS (
Carvedilol Prospective Randomized Cumulative Survival) trial.
beta-Adrenoceptor antagonists reduce perioperative mortality in patients undergoing cardiac as well as non-cardiac surgery; however, they remain underutilised.
Contraindications to
beta-adrenoceptor antagonist therapy include severe
bradycardia, high-grade
atrioventricular block, marked
sinus node dysfunction and acute exacerbations of
heart failure. Many of the perceived adverse effects of
beta-adrenoceptor antagonists have not been substantiated by large clinical trials.
beta-Adrenoceptor antagonists differ with regard to receptor selectivity, receptor affinity, lipophilicity and intrinsic
sympathomimetic activity. Beneficial properties of
beta-adrenoceptor antagonists may not always be extrapolated as a class effect, and patient selection and
drug preparations should follow trial guidelines. The beneficial effects of
beta-adrenoceptor antagonists are clearly proven in cardiac patients and those at risk for
cardiac disease. They are indicated for
heart failure and proven beneficial in patients undergoing cardiac and non-cardiac surgery. These benefits appear to be consistent across most patient subgroups.
beta-Adrenoceptor antagonists are generally well tolerated, yet significant morbidity and mortality result from their continued underutilisation.