Beta-blockers in COPD: time for reappraisal

Lipworth, Brian J.; Wedzicha, Jadwiga A.; Devereux, Graham; Vestbo, Jørgen; Dransfield, Mark T.

doi:10.1183/13993003.01847-2015

Cited by 67 publications

(59 citation statements)

References 81 publications

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“…Because of different mechanisms of action, the combination of these drugs is expected to be more effective than the individual components in the maintenance treatment of COPD [1]. Evidence available from randomised controlled trails and observational studies on increased risk of cardiovascular adverse events is large but difficult to summarise because of complex methodology, different comparison groups and potential bias in each study [2][3][4][5]. Results are controversial and inconclusive.…”

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confidence: 99%

COPD and bronchodilators: should the heart pay the bill for the lung?

Agabiti¹,

Corbo

2017

Eur Respir J

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@ERSpublications Treatment with bronchodilators in COPD patients should take into account cardiovascular comorbidities http://ow.ly/gMIG30aAwTKCite this article as: Agabiti N, Corbo GM. COPD and bronchodilators: should the heart pay the bill for the lung? Eur Respir J 2017; 49: 1700370 [https://doi.org/10.1183/13993003.00370-2017. The questionThe pharmacological treatment of patients with coexisting cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) is challenging, because some drugs for COPD patients should be used with caution in patients with CVD, and vice versa. The crucial question on cardiovascular safety of long-acting bronchodilators, i.e. long-acting β 2 -agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs, principally tiotropium), has no definitive answer. Because of different mechanisms of action, the combination of these drugs is expected to be more effective than the individual components in the maintenance treatment of COPD [1]. Evidence available from randomised controlled trails and observational studies on increased risk of cardiovascular adverse events is large but difficult to summarise because of complex methodology, different comparison groups and potential bias in each study [2][3][4][5]. Results are controversial and inconclusive. The risks of combining LABAs and tiotropium for the treatment of COPD are still unclear. Whether COPD patients treated with long-acting bronchodilators have increased risk of heart failure, or patients with both COPD and heart failure have higher risk of adverse events, remain open questions. What the study addsIn this issue of the European Respiratory Journal, the study presented by SUISSA et al.[6] interestingly contributes to the ongoing debate. The focus is on the concurrent use of long-acting bronchodilators. A large COPD patient cohort was selected from the UK Clinical Practice Research Datalink for 2002-2012 and followed up over 1 year. Compared with monotherapy, adding a second long-acting bronchodilator (either a LABA or tiotropium) did not increase the risk of myocardial infarction, stroke or arrhythmia. However, a statistically significant 16% increase in the risk of heart failure was found with the addition of a second long-acting bronchodilator rather than monotherapy; the increase was higher (23%) when patients with previous diagnosis of heart failure (about 3% of the whole study population) were excluded. Large numbers from real-world settings, sophisticated analytical approaches and sensitivity analyses led to robust results, considering the known limits of observational studies on the comparative effectiveness and safety of drugs. The fact that the use of two long-acting bronchodilators was found to be safe, in terms of major cardiovascular events, is reassuring and supports the guidelines/recommendations regarding the use of fixed-dose combination bronchodilators. However, the effect on heart failure is relevant and deserves some additional consideration.

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confidence: 99%

COPD and bronchodilators: should the heart pay the bill for the lung?

Agabiti¹,

Corbo

2017

Eur Respir J

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“…In this issue of the European Respiratory Journal, LIPWORTH et al [5] provide a comprehensive summary on the use of beta-blockers in patients with COPD. In their narrative review, the authors disentangled the complex links between COPD and the heart, reviewed the available data on the use of beta-blockers for reducing exacerbations and mortality, and summarised the unmet needs in the field, with special reference to a more in-depth knowledge of how different beta-blockers can affect pulmonary function based on their pharmacology.…”

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confidence: 99%

“…Another point examined by LIPWORTH et al [5] is the potential crossover efficacy between systemic beta-blockers and inhaled medications. Pharmacological treatment of COPD exerts beneficial effects on both cardiac function and lung vasculature, which may in turn contribute to the favourable effects of inhaled therapies [28].…”

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confidence: 99%

Beta-blockers and COPD: the show must go on

2016

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@ERSpublications Current evidence on beta-blockers efficacy and safety in COPD is encouraging but limited with future studies needed http://ow.ly/IaNL301YANIIdentification of comorbidities is now recognised as one of the pillars for a comprehensive clinical evaluation in chronic obstructive pulmonary disease (COPD) [1]. Specifically, the burden of coexisting cardiovascular disease in COPD has gained significant attention, with specific algorithms being developed for its clinical detection [2]. The relationship between the heart and COPD is of clinical relevance not only for the well-documented relationship between the two organs [3], but also for the potential mutual influence of treatments. The interactions between oral beta-blockers and inhaled β-adrenergic drugs pose significant challenges for clinicians involved in the management of patients with chronic cardiorespiratory conditions. In particular, the use of beta-blockers in COPD remains the subject of ongoing controversy [4].In this issue of the European Respiratory Journal, LIPWORTH et al.[5] provide a comprehensive summary on the use of beta-blockers in patients with COPD. In their narrative review, the authors disentangled the complex links between COPD and the heart, reviewed the available data on the use of beta-blockers for reducing exacerbations and mortality, and summarised the unmet needs in the field, with special reference to a more in-depth knowledge of how different beta-blockers can affect pulmonary function based on their pharmacology. Despite published reports of physicians being reluctant to prescribe beta-blockers in COPD patients with a history of myocardial infarction or coexisting heart failure, the authors conclude that there are compelling reasons for the use of cardioselective beta-blockers in this patient group.In order to understand the potential implications of beta-blockers on COPD a brief review of the lung innervation and anatomical distribution of receptors in the lung is required. In humans, the direct sympathetic innervation of the airway smooth muscle is very poor [6]. Somewhat counterintuitively, however, the density of β-adrenergic receptors is markedly high and their expression can be identified in different cell types. In the human lung, β-adrenergic receptors on smooth muscle, epithelial and mast cells are of the β 2 -subtype, whose density increases towards the peripheral airways. By contrast, human submucosal glands and alveolar wall cells also express β 1 -receptors [7,8]. In the healthy heart, β 1 -and β 2 -adrenergic receptors coexist in a 4:1 ratio. However, in the failing heart, β 1 -adrenergic receptor numbers decrease, paralleled by an increase in β 2 -adrenergic receptors, ultimately resulting in a 3:2 ratio [9]. In this scenario, the occurrence of interactions may not be negligible. In general, the effects of drugs that act on adrenergic receptors depend both on the intrinsic pharmacological properties of the drug (including the β 1 /β 2 ratio) and its bioavailability (intended to be high in systemic beta-b...

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“…Among patients with known coronary arterial disease the mortality reduction was 39% and in heart failure was 26%. However, it remains unclear if beta-blockers may reduce exacerbations or mortality in individuals with COPD who have covert (untreated or unrecognized) cardiovascular disease (12). Prior to assessing this, which would require a longer study, a prospective trial is required to address concerns over potential beta blocker induced bronchoconstriction.…”

Section: Introductionmentioning

confidence: 99%

“…ICS/LABA vs ICS). It should be noted that whilst ICS only therapy is not licensed in COPD, in real life 8% of patients are taking such treatment (14).…”

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confidence: 99%