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

Abstract

Abstract Abstract. Objectives. The purpose of this study was to determine the respiratory, hemodynamic, and clinical effects of switching between β1-selective and nonselective β-blockers in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). Background. Carvedilol, metoprolol succinate, and bisoprolol are established β-blockers for treating CHF. Whether differences in β-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 patients receiving optimal therapy for CHF was conducted in two Australian teaching hospitals. Participants received each β-blocker, dose-matched, for 6 weeks before resuming their original β-blocker. Echocardiography, N-terminal pro-hormone brain natriuretic peptide (NT-ProBNP), central augmented pressure from pulse waveform analysis, respiratory function testing, 6-minute walk distance, and New York Heart Association (NYHA) functional class were assessed at each visit. Results. Of 51 patients 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. NT-ProBNP was significantly lower with carvedilol than with metoprolol or bisoprolol (mean, carvedilol 1001 [95% confidence interval (CI), 633–1367] ng/L; metoprolol 1371 [95% CI, 778–1964] ng/L; bisoprolol 1349 [95% CI, 782–1916] ng/L; P<.01), and returned to baseline level on resumption of the initial β-blocker. Central augmented pressure, a measure of pulsatile afterload, was lowest with carvedilol (carvedilol 9.9 [95% CI, 7.7–12.2] mm Hg; metoprolol 11.5 [95% CI, 9.3–13.8] mm Hg; bisoprolol 12.2 [95% CI, 9.6–14.7] mm Hg; P<.05). In patients with COPD, forced expiratory volume in 1 second (FEV1) was lowest with carvedilol and highest with bisoprolol (carvedilol 1.85 [95% CI, 1.67–2.03] l/s; metoprolol 1.94 [95% CI, 1.73–2.14] l/s; bisoprolol 2.0 [95% CI, 1.79–2.22] l/s; P<.001). The NYHA functional class, 6-minute walk distance, and left ventricular ejection fraction did not change. The β-blocker switches were well tolerated. Conclusions. Switching between β1-selective β-blockers and the nonselective β-blocker carvedilol is well tolerated but results in demonstrable changes in airway function, most marked in patients with COPD. Switching from β1-selective β-blockers to carvedilol causes short-term reduction of central augmented pressure and NT-ProBNP.—Jabbour A, Macdonald PS, Keogh AM, et al. Differences between β-blockers in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized crossover trial. J Am Coll Cardiol. 2010;55:1780-1787.