Differences Between Beta-Blockers in Patients With Chronic Heart Failure and Chronic Obstructive Pulmonary Disease: A Randomized Crossover Trial

• Published in: Journal of the American College of Cardiology 2010-04, Vol.55 (17), p.1780-1787
• Main Authors: JABBOUR, Andrew, MACDONALD, Peter S, KEOGH, Anne M, KOTLYAR, Eugene, MELLEMKJAER, Soren, COLEMAN, Cathie F, ELSIK, Maros, KRUM, Henry, HAYWARD, Christopher S
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - therapeutic use; Adult; Aged; Aged, 80 and over; Beta blockers; Biological and medical sciences; Bisoprolol - therapeutic use; Carbazoles - therapeutic use; Cardiology; Cardiology. Vascular system; Chronic Disease; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Confidence intervals; Cross-Over Studies; Drug therapy; Echocardiography; Female; Heart; Heart failure; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart rate; Humans; Male; Medical sciences; Metoprolol - analogs & derivatives; Metoprolol - therapeutic use; Middle Aged; Natriuretic Peptide, Brain - blood; Pneumology; Propanolamines - therapeutic use; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulse; Respiratory Function Tests; Walking
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2010.01.024

The purpose of this study was to determine the respiratory, hemodynamic, and clinical effects of switching between beta1-selective and nonselective beta-blockers in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). 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. 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. 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 pro-hormone 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. Switching between beta1-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 beta1-selective