Beta-blocker therapy in patients with COPD: a systematic literature review and meta-analysis with multiple treatment comparison

Abstract

Background Beta-blockers are associated with reduced mortality in patients with cardiovascular disease but are often under prescribed in those with concomitant COPD, due to concerns regarding respiratory side-effects. We investigated the effects of beta-blockers on outcomes in patients with COPD and explored within-class differences between different agents. Methods We searched the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Medline for observational studies and randomized controlled trials (RCTs) investigating the effects of beta-blocker exposure versus no exposure or placebo, in patients with COPD, with and without cardiovascular indications. A meta-analysis was performed to assess the association of beta-blocker therapy with acute exacerbations of COPD (AECOPD), and a network meta-analysis was conducted to investigate the effects of individual beta-blockers on FEV1. Mortality, all-cause hospitalization, and quality of life outcomes were narratively synthesized. Results We included 23 observational studies and 14 RCTs. In pooled observational data, beta-blocker therapy was associated with an overall reduced risk of AECOPD versus no therapy (HR 0.77, 95%CI 0.70 to 0.85). Among individual beta-blockers, only propranolol was associated with a relative reduction in FEV1 versus placebo, among 199 patients evaluated in RCTs. Narrative syntheses on mortality, all-cause hospitalization and quality of life outcomes indicated a high degree of heterogeneity in study design and patient characteristics but suggested no detrimental effects of beta-blocker therapy on these outcomes. Conclusion The class effect of beta-blockers remains generally positive in patients with COPD. Reduced rates of AECOPD, mortality, and improved quality of life were identified in observational studies, while propranolol was the only agent associated with a deterioration of lung function in RCTs.

Beta-Blockers in High-Risk Outpatients with Chronic Obstructive Pulmonary Disease are Associated with All-Cause Mortality – The STATUETTE Cohort Study

“…Other observational studies report reduced mortality, and a recent meta-analysis concludes a general tendency towards reduced risk of mortality. 15 Differing results might depend on study population factors, such as disease severity and treatment, with both Ekström et al 27 and the present study primarily including patients with advanced COPD. Furthermore, differences in study design, including adjustment for immortal time bias, may very well explain differing results, as immortal time bias often leads to intervention risk reduction in pharmacoepidemiologic studies.…”

“…The present study, and the lack of association found between beta-blocker use and AECOPD risk, is in discordance with previous meta-analyses and observational studies reporting an association between use of beta-blockers and a reduced risk of exacerbations. 15,24 The nationwide Danish publication by Rasmussen et al 25 reported an association between beta-blocker use and reduced risk of exacerbations in COPD patients following hospitalization with a diagnosis of AMI. In contrast, the RCT BLOCK COPD 13 included patients without CVD and reported an increased risk of severe AECOPD (but not time to exacerbation) in beta-blocker users.…”

“…[11][12][13] While a recent randomized, placebo-controlled clinical trial on metoprolol in COPD without concomitant CVD (BLOCK COPD 14 ) was terminated early due to futility and patient-reported adverse events, retrospective observational studies have reported the benefits of beta-blocker treatment on COPD-related outcomes, such as exacerbations and mortality. 15 As such, findings on the potential risks and/or benefits of beta-blocker use in COPD vary with study design, outcomes and populations chosen, further complicating the already difficult task of providing optimal treatment for COPD and related comorbidities.…”

Impact of COPD and asthma on in-hospital mortality and management of patients with heart failure in England and Wales: an observational analysis

“…Those with asthma-HFrEF had 43% less chance of being prescribed a beta-blocker compared with patients with HF-alone. Current guidelines recommend that asthma patients with chronic HFrEF should not receive disease-modifying beta-blocker treatment due to possible bronchoconstriction, despite evidence to suggest that cardioselective beta-blockade may be used with careful up-titration and monitoring,30 31 where benefits may outweigh risks in individual patients. Based on the low uptake across the whole spectrum of HF medications in patients with additional lung disease (figure 3), we expect these patients would have worse prognosis compared with their more adequately treated counterparts.…”

β-Blockers and the Risk of New-Onset Depression

“…26 However, an analysis of linked data from the UK Clinical Practice Research Datalink found that cardioselective BBs, unlike nonselective BBs, were not associated with the risk of moderate or severe exacerbation of asthma in patients with cardiovascular disease and comorbid asthma. 27 Furthermore, in a systematic review and multiple treatment comparison meta-analysis of 23 observational studies and 14 RCTs, Gulea et al 28 found that only propranolol was associated with reduced forced expiratory volume during the first second (FEV1); otherwise, relative to no treatment, BB treatment was actually associated with a reduced risk of acute exacerbation of chronic obstructive pulmonary disease events (hazard ratio, 0.77; 95% CI, 0.70-0.85). A qualitative analysis of the data in this study suggested no detrimental effect of BBs on quality of life, all-cause hospitalization, and mortality outcomes.…”