Beta-adrenoceptor antagonists in elderly patients with chronic heart failure: therapeutic potential of third-generation agents

Abstract

Chronic heart failure (CHF) is a common and disabling condition with an incidence and prevalence that increase sharply with age. The median age of presentation of new heart failure cases is > 75 years. Effective treatments, including beta-adrenoceptor antagonists, have been proven in randomised, controlled trials. The average age in these placebo-controlled mortality and morbidity studies of beta-adrenoceptor antagonists in heart failure has, however, been < 63 years, and all patients with an ejection fraction > or = 40% were excluded. This lack of a representative sample of elderly patients with heart failure has raised concerns about extrapolating the available evidence for beta-adrenoceptor antagonists to a more elderly heart failure population. Beta-adrenoceptor antagonists may have a less beneficial effect or even an adverse effect in elderly heart failure patients. There is evidence that beta-adrenoceptor antagonists are less frequently prescribed in elderly CHF patients, and that this lack of treatment is associated with impaired outcomes. Establishing which beta-adrenoceptor antagonists, if any, are effective in elderly CHF is therefore of extreme importance. The elderly have a reduced cardiovascular reserve and may be less tolerant of the introduction of a vasoconstricting beta-adrenoceptor antagonist. In addition, the higher proportion of elderly CHF patients with relatively preserved systolic function (for which no treatment has been proven to reduce mortality and morbidity) means that we cannot say with certainty that beta-adrenoceptor antagonists have been proven to be effective in a general elderly CHF population. Third-generation beta-adrenoceptor antagonists with vasodilating actions in addition to their beta-adrenoceptor antagonist effects may offer several theoretical advantages over earlier beta-adrenoceptor antagonists for elderly CHF patients. Three of this class (carvedilol, bucindolol and nebivolol) have been evaluated with respect to their efficacy in reducing mortality and morbidity in CHF, and only two of these (carvedilol and nebivolol) had a proven outcome benefit in a properly powered randomised, controlled trial. Only the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (which used the vasodilating third-generation beta-adrenoceptor antagonist nebivolol) has prospectively investigated the treatment of CHF in elderly patients, including those with preserved systolic function, and demonstrated a significant reduction in the risk of death or cardiovascular hospitalisation. In conclusion, prescribers are advised that nebivolol should be preferred in elderly patients with CHF, because of its proven efficacy in a representative group of elderly CHF patients.