Differences between beta-blockers in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized crossover trial.
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 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).
Jabbour A
，Macdonald PS
，Keogh AM
，Kotlyar E
，Mellemkjaer S
，Coleman CF
，Elsik M
，Krum H
，Hayward CS
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Prognostic Benefits of Carvedilol, Bisoprolol, and Metoprolol Controlled Release/Extended Release in Hemodialysis Patients with Heart Failure: A 10-Year Cohort.
Heart failure is a highly prevalent cardiovascular complication among patients receiving long-term hemodialysis, but the benefits of carvedilol, bisoprolol, and metoprolol controlled release/extended release on the outcomes of these patients remain unclear. In this study, we address the use of these 3 β-blockers and their associations with mortality.
Long-term hemodialysis patients, aged ≥35 years, with new-onset heart failure and receiving various medications were identified through the use of 1999-2010 data from the Taiwan National Health Insurance Research Database. From the total of 4435 heart failure patients, we selected 1700 new users of the 3 β-blockers (study group) and 1700 nonusers (control group), by using matched cohorts according to their propensity scores, and then compared the 5-year all-cause mortality rates by using Cox proportional hazard regressions and time-dependent covariate adjustment. During 3944 person-years of follow-up, 666 (39.2%) deaths occurred within the study group, compared with 918 (54%) deaths during 2893 person-years of follow-up in the control group. The 5-year mortality rate for the study (control) group was 54.5% (70.3%); P<0.001. Adjusted hazard regression analyses revealed that the therapeutic effects of β-blockers remained significant for all-cause mortality (hazard ratio 0.80, 95% CI 0.72 to 0.90). Subgroup analyses revealed that patients in the study group receiving β-blockers plus renin-angiotensin system antagonists exhibited the lowest mortality rate, while the highest mortality rate was found among patients in the control group receiving neither β-blockers nor renin-angiotensin system antagonists.
This study demonstrates that the 3 β-blockers were associated with improved survival in long-term hemodialysis patients with heart failure.
Tang CH
，Wang CC
，Chen TH
，Hong CY
，Sue YM
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《Journal of the American Heart Association》
Differences between bisoprolol and carvedilol in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized trial.
Chronic obstructive pulmonary disease (COPD) frequently coexists in patients with chronic heart failure (CHF) and is a key factor for beta blocker underprescription and underdosing. This study compared effects of bisoprolol and carvedilol in patients with both conditions.
This was a randomized open-label study, of bisoprolol and carvedilol during initiation and uptitration to target or maximal tolerated dose. Pulmonary function testing, 12-lead electrocardiogram, and N-terminal pro brain natriuretic peptide were measured at baseline and follow-up.
We randomized 63 elderly patients (73 ± 9 years, 81% men, left ventricular ejection fraction 33 ± 7%) with mild to moderate CHF (54% New York Heart Assocation class II) and moderate to severe COPD (76% Global initiative for chronic Obstructive Lung Disease stage 2). Target dose was tolerated by 31 (49%) patients and 19 (30%) patients experienced adverse events during follow-up (19% bisoprolol, 42% carvedilol, p = 0.045). Study medication had to be withdrawn in 8 (13%) patients (bisoprolol: 2 due to hypotension, 1 due to bradycardia; carvedilol: 2 due to hypotension and 1 due to wheezing, dyspnoea, and oedema, respectively). Forced expiratory volume in 1(st) second significantly increased in bisoprolol (1561 ± 414 ml to 1698 ± 519 ml, p = 0.046) but not carvedilol (1704 ± 484 to 1734 ± 548, p = 0.44) group. Both agents reduced heart rate (bisoprolol: 75 ± 14 to 68 ± 10, p = 0.007; carvedilol 78 ± 14 to 72 ± 12, p = 0.016) and had no effect on N-terminal pro brain natriuretic peptide.
Beta blockers frequently caused adverse events, and thus 49% of patients could tolerate the target dose. Bisoprolol induced demonstrable improvement in pulmonary function and caused less adverse events.
Lainscak M
，Podbregar M
，Kovacic D
，Rozman J
，von Haehling S
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