Krukemyer J J
Department of Clinical Pharmacy, University of Tennessee, Memphis 38163.
Clin Pharm. 1990 Nov;9(11):853-63.
The use of beta-adrenergic blocking agents in patients with congestive heart failure (CHF) is reviewed. The sympathetic nervous system plays an important compensatory role in maintaining inotropic support of the failing heart; therefore, beta blockers have long been considered contraindicated in CHF patients. However, prolonged excessive activation of the sympathetic nervous system may be detrimental. Several clinical trials have shown improved functional status and hemodynamic indices in some patients with dilated cardiomyopathy who received beta blockers. The maximum effect required up to 12 months. Two studies also showed trends toward improved survival. Aspects of study design that appear to be associated with the observation of a favorable response to beta blockade in CHF patients are a low initial dosage, gradual adjustment of the dosage, and a sufficient duration of therapy. Trials with unfavorable results lacked one or more of those design characteristics. Mechanisms proposed to underlie the beneficial effects of beta blockers in CHF patients include up-regulation of beta-receptors, reduction in cardiac energy requirements, protection of the myocardium against norepinephrine toxicity, and anti-arrhythmic effects. Most studies were conducted in patients with idiopathic dilated cardiomyopathy; it is unknown whether beta-blocker therapy is equally beneficial in patients with CHF arising from other causes. Metoprolol is the agent for which there is the most experience; comparative efficacy trials have not been conducted. Beta-adrenergic blockers appear to be beneficial in some patients with CHF. Further trials are needed to identify the patients most likely to respond and the drugs most likely to work.
本文综述了β肾上腺素能阻滞剂在充血性心力衰竭(CHF)患者中的应用。交感神经系统在维持衰竭心脏的心肌收缩力方面发挥着重要的代偿作用;因此,长期以来β阻滞剂一直被认为是CHF患者的禁忌药物。然而,交感神经系统的长期过度激活可能是有害的。几项临床试验表明,一些扩张型心肌病患者接受β阻滞剂治疗后,其功能状态和血流动力学指标有所改善。最大疗效需要长达12个月才能显现。两项研究还显示出生存率提高的趋势。在CHF患者中,似乎与观察到对β阻滞剂有良好反应相关的研究设计方面包括低初始剂量、逐渐调整剂量以及足够的治疗持续时间。结果不佳的试验缺乏这些设计特征中的一项或多项。提出的β阻滞剂对CHF患者有益作用的潜在机制包括β受体上调、降低心脏能量需求、保护心肌免受去甲肾上腺素毒性以及抗心律失常作用。大多数研究是在特发性扩张型心肌病患者中进行的;β阻滞剂治疗对其他原因引起的CHF患者是否同样有益尚不清楚。美托洛尔是使用经验最多的药物;尚未进行比较疗效试验。β肾上腺素能阻滞剂似乎对一些CHF患者有益。需要进一步试验来确定最可能有反应的患者以及最可能有效的药物。