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

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Objectives

The purpose of this study was to determine the respiratory, hemodynamic, and clinical effects of switching between β1-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 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.

Conclusions

Switching between β1-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 β1-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)

Key Words

heart failure
chronic obstructive pulmonary disease
beta-blocker

Abbreviations and Acronyms

B1B
β1-selective beta-blockers
CHF
chronic heart failure
CI
confidence interval
COPD
chronic obstructive pulmonary disease
FEV1
forced expiratory volume in 1 s
FVC
forced vital capacity
NT-proBNP
N-terminal pro-hormone brain natriuretic peptide
NYHA
New York Heart Association
6MWD
6-min walk distance

Cited by (0)

This study was supported by an unrestricted education grant (“Cardiovascular Lipid” Grant) from Pfizer Australia(West Ryde, New South Wales, Australia) to the principal investigator Assoc. Prof. Hayward. The funding source had no role in the design, conduct, data analysis, or reporting of this study or in the decision to submit the manuscript for publication. Dr. Jabbour has received minor honoraria and educational financial support from AstraZeneca, Roche, and Alpha-Pharma. Dr. Macdonald has received speaker fees from AstraZeneca, Actelion Janssen-Cilag, Novartis, and Pfizer. Dr. Keogh has received trial funding from Actelion, Myogen, Gilead, Pfizer, GlaxoSmithKline, Venragr, Heartware, Novartis, Roche, Bayer, and Schering. Dr. Kotlyar has received honoraria for speaking engagements from Alpha-Pharma and AstraZeneca. Dr. Krum has received grant funding from Roche, Alpha-Pharma, and Merck CSL. Assoc. Prof. Hayward has received grant funding from Pfizer, and honoraria/travel grants from AstraZeneca, Roche, and Alpha-Pharma, CSL Biotherapies, and Merck.