Coats Andrew J S
Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
Drugs Aging. 2006;23(2):93-9. doi: 10.2165/00002512-200623020-00001.
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.
慢性心力衰竭（CHF）是一种常见且使人衰弱的疾病，其发病率和患病率随年龄急剧上升。新诊断心力衰竭病例的中位年龄>75岁。包括β-肾上腺素能受体拮抗剂在内的有效治疗方法已在随机对照试验中得到证实。然而，在这些关于β-肾上腺素能受体拮抗剂治疗心力衰竭的安慰剂对照死亡率和发病率研究中，患者的平均年龄<63岁，且所有射血分数≥40%的患者均被排除。缺乏老年心力衰竭患者的代表性样本引发了人们对将β-肾上腺素能受体拮抗剂的现有证据外推至更年长心力衰竭人群的担忧。β-肾上腺素能受体拮抗剂在老年心力衰竭患者中可能疗效较差甚至产生不良反应。有证据表明，老年CHF患者中β-肾上腺素能受体拮抗剂的处方率较低，而这种治疗的缺乏与预后不良相关。因此，确定哪些β-肾上腺素能受体拮抗剂（如果有的话）对老年CHF有效至关重要。老年人的心血管储备功能下降，可能对引入具有血管收缩作用的β-肾上腺素能受体拮抗剂耐受性较差。此外，老年CHF患者中收缩功能相对保留的比例较高（尚无证据表明针对此类患者的治疗可降低死亡率和发病率），这意味着我们不能确定β-肾上腺素能受体拮抗剂已被证实在一般老年CHF人群中有效。除了具有β-肾上腺素能受体拮抗作用外还具有血管舒张作用的第三代β-肾上腺素能受体拮抗剂，相对于早期的β-肾上腺素能受体拮抗剂，可能为老年CHF患者带来一些理论上的优势。已对该类药物中的三种（卡维地洛、布新洛尔和奈必洛尔）在降低CHF死亡率和发病率方面的疗效进行了评估，其中只有两种（卡维地洛和奈必洛尔）在一项样本量充足的随机对照试验中被证明确实有益。只有老年心力衰竭患者奈必洛尔干预对结局和再住院影响的研究（该研究使用了具有血管舒张作用的第三代β-肾上腺素能受体拮抗剂奈必洛尔）前瞻性地研究了老年患者CHF的治疗，包括收缩功能保留的患者，并证明死亡或心血管住院风险显著降低。总之，建议处方医生，对于老年CHF患者，应首选奈必洛尔，因为其在一组具有代表性的老年CHF患者中已被证明确实有效。
