Differences Between Beta-Blockers in Patients With Chronic Heart Failure and Chronic Obstructive Pulmonary Disease A Randomized Crossover Trial
Differences Between Beta-Blockers in Patients With Chronic Heart Failure and Chronic Obstructive Pulmonary Disease A Randomized Crossover Trial
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DOI：
10.1016/j.jacc.2010.01.024
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发表时间：
2010-04-27
影响因子：
24
通讯作者：
Hayward, Christopher S.
中科院分区：
文献类型：
--
作者：
Jabbour, Andrew;Macdonald, Peter S.;Hayward, Christopher S.
目的 本研究的目的是确定慢性心力衰竭 (CHF) 和慢性阻塞性肺疾病 (COPD) 患者切换 β1 选择性和非选择性 β 受体阻滞剂的呼吸、血流动力学和临床效果。 背景 卡维地洛、琥珀酸美托洛尔和比索洛尔是治疗 CHF 的既定 β 受体阻滞剂。 β 受体特异性的差异是否会影响 CHF 患者（尤其是那些合并 COPD 的患者）的肺或血管功能，目前尚不完全确定。 方法 在 2 家澳大利亚教学医院进行了一项随机、开放标签、三重交叉试验，涉及 51 名接受 CHF 最佳治疗的受试者。受试者接受每种剂量匹配的 β 受体阻滞剂 6 周，然后再恢复原来的 β 受体阻滞剂。每次就诊时均评估超声心动图、N 端激素原脑钠肽、脉搏波形分析中枢增强压、呼吸功能测试、6 分钟步行距离和纽约心脏协会 (NYHA) 功能分级。 结果 51 名平均年龄为 66 +/- 12 岁的受试者，NYHA 功能分级 I (n = 6)、II (n = 29) 或 III (n = 16) 以及左心室射血分数平均值为 37 +/- 10%，其中 35 人患有慢性阻塞性肺病 (COPD)。卡维地洛组的 N 末端激素原脑钠肽显着低于美托洛尔或比索洛尔组（平均值：卡维地洛 1,001 [95% 置信区间 (CI)：633 至 1,367] ng/l；美托洛尔 1,371 [95% CI：778 至 1,964] ng/l；比索洛尔 1,349 [95% CI：782 至 1,916] ng/l；p < 0.01），并在恢复初始 β 受体阻滞剂后恢复至基线水平。中心增压压（衡量脉动后负荷的指标）使用卡维地洛最低（卡维地洛 9.9 [95% CI：7.7 至 12.2] mm Hg；美托洛尔 11.5 [95% CI：9.3 至 13.8] mm Hg；比索洛尔 12.2 [95% CI：9.6 至 14.7] mm Hg；p < 0.05）。在 COPD 受试者中，卡维地洛组 1 秒用力呼气量最低，比索洛尔组最高（卡维地洛 1.85 [95% CI：1.67 至 2.03] l/s；美托洛尔 1.94 [95% CI：1.73 至 2.14] l/s；比索洛尔 2.0 [95% CI：1.79 至 2.14] l/s） 2.22] 升/秒；p < 0.001）。 NYHA 功能分级、6 分钟步行距离和左心室射血分数没有变化。 β-受体阻滞剂的转换耐受性良好。结论 β1-选择性β-受体阻滞剂和非选择性β-受体阻滞剂卡维地洛之间的转换耐受性良好，但会导致气道功能发生明显变化，在 COPD 患者中最为明显。从 β1 选择性 β 受体阻滞剂转为卡维地洛会导致中枢增压压力和 N 端激素前脑钠尿肽短期降低。 （非选择性和 β1 选择性 β 受体阻滞剂对慢性稳定充血性心力衰竭患者呼吸和动脉功能以及心室动态的比较；澳大利亚新西兰临床试验注册中心，ACTRN12605000504617）（J Am Coll Cardiol 2010；55：1780-7）（C）2010 年，美国心脏病学会基金会
Objectives The purpose of this study was to determine the respiratory, hemodynamic, and clinical effects of switching between beta 1-selective and nonselective beta-blockers in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD).Background Carvedilol, metoprolol succinate, and bisoprolol are established beta-blockers for treating CHF. Whether differences in beta-receptor specificities affect lung or vascular function in CHF patients, particularly those with coexistent COPD, remains incompletely characterized.Methods A randomized, open label, triple-crossover trial involving 51 subjects receiving optimal therapy for CHF was conducted in 2 Australian teaching hospitals. Subjects received each beta-blocker, dose-matched, for 6 weeks before resuming their original beta-blocker. Echocardiography, N-terminal pro-hormone brain natriuretic peptide, central augmented pressure from pulse waveform analysis, respiratory function testing, 6-min walk distance, and New York Heart Association (NYHA) functional class were assessed at each visit.Results Of 51 subjects with a mean age of 66 +/- 12 years, NYHA functional class I (n = 6), II (n = 29), or III (n = 16), and left ventricular ejection fraction mean of 37 +/- 10%, 35 had coexistent COPD. N-terminal prohormone brain natriuretic peptide was significantly lower with carvedilol than with metoprolol or bisoprolol (mean: carvedilol 1,001 [95% confidence interval (CI): 633 to 1,367] ng/l; metoprolol 1,371 [95% CI: 778 to 1,964] ng/l; bisoprolol 1,349 [95% CI: 782 to 1,916] ng/l; p < 0.01), and returned to baseline level on resumption of the initial beta-blocker. Central augmented pressure, a measure of pulsatile afterload, was lowest with carvedilol (carvedilol 9.9 [95% CI: 7.7 to 12.2] mm Hg; metoprolol 11.5 [95% CI: 9.3 to 13.8] mm Hg; bisoprolol 12.2 [95% CI: 9.6 to 14.7] mm Hg; p < 0.05). In subjects with COPD, forced expiratory volume in 1 s was lowest with carvedilol and highest with bisoprolol (carvedilol 1.85 [95% CI: 1.67 to 2.03] l/s; metoprolol 1.94 [95% CI: 1.73 to 2.14] l/s; bisoprolol 2.0 [95% CI: 1.79 to 2.22] l/s; p < 0.001). The NYHA functional class, 6-min walk distance, and left ventricular ejection fraction did not change. The beta-blocker switches were well tolerated.Conclusions Switching between beta 1-selective beta-blockers and the nonselective beta-blocker carvedilol is well tolerated but results in demonstrable changes in airway function, most marked in patients with COPD. Switching from beta 1-selective beta-blockers to carvedilol causes short-term reduction of central augmented pressure and N-terminal pro-hormone brain natriuretic peptide. (Comparison of Nonselective and Beta1-Selective Beta-Blockers on Respiratory and Arterial Function and Cardiac Chamber Dynamics in Patients With Chronic Stable Congestive Cardiac Failure; Australian New Zealand Clinical Trials Registry, ACTRN12605000504617) (J Am Coll Cardiol 2010; 55: 1780-7) (C) 2010 by the American College of Cardiology Foundation