beta-Adrenoceptor antagonists in elderly patients with heart failure: a critical review of their efficacy and tolerability.

Heart failure (HF) is a major public health problem among the elderly. The syndrome of HF may arise in the presence of either a depressed or apparently normal left-ventricular ejection fraction (LVEF). The latter entity is more common in the elderly. In elderly patients with HF, prescription of a beta-adrenoceptor antagonist may raise concerns regarding efficacy and tolerability. Because of these concerns, but also as a result of a paucity of published data, beta-adrenoceptor antagonists are under-prescribed to elderly patients with HF in general practice. We review the evidence regarding the efficacy and tolerability of beta-adrenoceptor antagonist therapy in elderly patients with HF. We found three major sources of evidence: one prospective, randomised controlled trial (RCT), SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure); a subgroup meta-analysis of elderly patients included in systolic HF trials; and a large number of observational studies. SENIORS showed that the third-generation beta-adrenoceptor antagonist nebivolol reduces the risk of all-cause mortality or cardiovascular admission in elderly patients (aged > or =70 years) with HF and a broad range of LVEF. The subgroup meta-analysis of RCTs showed that beta-adrenoceptor antagonists reduce mortality in elderly patients (aged 60-80 years) with systolic HF, and that the benefit is similar to that observed in non-elderly patients (aged <60 years). The observational studies showed a beneficial effect of beta-adrenoceptor antagonists in elderly populations in daily practice, including those with depressed and preserved LVEF. However, the effect of beta-adrenoceptor antagonists on all-cause mortality may be lower in very elderly patients (aged >75 years). Approximately two-thirds of elderly patients with HF tolerate a beta-adrenoceptor antagonist, but only 40-70% of the target doses recommended in RCTs are achieved. Some clinical variables may predict low beta-adrenoceptor antagonist tolerability, such as low systolic blood pressure, higher New York Heart Association HF severity class, advanced age and ischaemic cause of HF. Furthermore, prescription of a high diuretic dose and calcium channel antagonists may also decrease beta-adrenoceptor antagonist tolerability. However, it is difficult to identify on clinical grounds patients intolerant to any beta-adrenoceptor antagonist dose. Low-dose therapy (<50% target dose) may be effective in an elderly population with HF, but prescription of at least a medium dose (> or =50% target dose) may achieve a higher benefit. In conclusion, although elderly patients with HF take lower doses of beta-adrenoceptor antagonists, these agents are still effective and overall well tolerated in this population. Elderly patients with HF should therefore not be denied beta-adrenoceptor antagonist therapy. The dilemma relies on dose-benefit balance, as higher doses would be more effective but may raise tolerability concerns. The beneficial effects of use of beta-adrenoceptor antagonists in elderly patients with HF and preserved LVEF need to be further confirmed in large RCTs.