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Lookup NU author(s): Professor Anthony De SoyzaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Observational studies of people with chronic obstructive pulmonary disease using beta-blockers for cardiovascular disease indicate that beta-blocker use is associated with reduced risk of chronic obstructive pulmonary disease exacerbation. However, at the time this study was initiated, there had been no randomised controlled trials confirming or refuting this. Objective(s): To determine the clinical and cost-effectiveness of adding bisoprolol (maximal dose 5 mg once daily) to usual chronic obstructive pulmonary disease therapies in patients with chronic obstructive pulmonary disease at high risk of exacerbation. Design: A multicentre, pragmatic, double-blind, randomised, placebo-controlled clinical trial. Setting: Seventy-six United Kingdom primary and secondary care sites. Participants: People aged ≥ 40 years with a diagnosis of at least moderately severe chronic obstructive pulmonary disease with a history of at least two exacerbations in the previous year. Interventions: Participants were randomised (1 : 1) to receive either bisoprolol or placebo for 1 year. During a 4- to 7-week titration period, the maximum tolerated dose was established (1.25 mg, 2.5 mg, 3.75 mg, 5 mg once daily). Primary outcome: A number of participant-reported exacerbations during the 1-year treatment period. Results: In total, 519 participants were recruited and randomised. Four post-randomisation exclusions left 259 in the bisoprolol group and 256 in the placebo group. Treatment groups were balanced at baseline: mean (standard deviation) age 68 (7.9) years; 53% men; mean (standard deviation) pack year smoking history 45 (25.2); mean (standard deviation) 3.5 (1.9) exacerbations in previous year. Primary outcome data were available for 99.8% of participants (bisoprolol 259, placebo 255). The mean (standard deviation) number of exacerbations was 2.03 (1.91) in the bisoprolol group and 2.01 (1.75) in the placebo group (adjusted incidence rate ratio 0.97, 95% confidence interval 0.84 to 1.13), p = 0.72. The number of participants with serious adverse events was similar between the two groups (bisoprolol 37, placebo 36). The total number of adverse reactions was also similar between the two groups. As expected, bisoprolol was associated with a higher proportion of vascular adverse reactions (e.g. hypotension, cold peripheries) than placebo, but was not associated with an excess of other adverse reactions, including those classified as respiratory. Adding bisoprolol resulted in a statistically insignificant trend towards higher costs (£636, 95% confidence interval £118 to £1391) and fewer quality-adjusted life-years (0.035, 95% confidence interval 0.059 to 0.010) compared to placebo. Limitations: The study findings should be interpreted with caution as the target sample size of 1574 was not achieved because the funder considered the study to be unviable in the COVID-19 pandemic clinical research environment. Although 28% of participants did not initiate bisoprolol/placebo (1.6%) or ceased during the treatment period (26.2%), this is consistent with similar trials in the United Kingdom. Conclusions: In this underpowered study, the addition of bisoprolol to usual chronic obstructive pulmonary disease treatment did not reduce the likelihood of exacerbations, and bisoprolol cannot be recommended as a treatment for chronic obstructive pulmonary disease. Future work: To incorporate definitive statements into appropriate clinical guidelines about the safety of bisoprolol for cardiovascular indications in people with chronic obstructive pulmonary disease. Trial registration: This trial is registered as ISRCTN10497306. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/130/20) and is published in full in Health Technology Assessment; Vol. 29, No. 17. See the NIHR Funding and Awards website for further award information.Chronic obstructive pulmonary disease is a lung disease causing shortness of breath. It has no cure and is a leading cause of death. It affects about 1.2 million people in the United Kingdom and costs the National Health Service around £1.9B each year. People with chronic obstructive pulmonary disease often have symptom ‘flare-ups’ (exacerbations) that usually need emergency treatment and impact the quality of life. Bisoprolol is usually used to treat cardiovascular diseases such as high blood pressure and heart failure. In observational research, people with chronic obstructive pulmonary disease who take beta-blockers have been reported to have a reduced chance of having exacerbations. The bisoprolol in chronic obstructive pulmonary disease study tested whether adding bisoprolol to usual chronic obstructive pulmonary disease treatments reduced exacerbations in people with chronic obstructive pulmonary disease. A total of 515 people with chronic obstructive pulmonary disease from 76 hospitals and general practitioner practices across the United Kingdom took part in the bisoprolol in chronic obstructive pulmonary disease study. They were randomly divided into two groups: one group (259 people) took bisoprolol pills every day and the other group (256 people) took dummy pills. People did not know which group they were in. We followed people for up to 12 months and counted how many exacerbations they had. In both groups, people had on average two exacerbations in 12 months. There was no difference between the groups – so bisoprolol did not reduce the number of exacerbations that people had. The bisoprolol group did not have any more serious adverse events or respiratory side effects than the placebo group. The COVID-19 pandemic had a major impact on the bisoprolol in chronic obstructive pulmonary disease study: we planned to recruit 1574 patients but were only able to recruit 515; so, the results have to be interpreted with some caution. Nevertheless, the results from the bisoprolol in chronic obstructive pulmonary disease study are important. Although bisoprolol did not reduce exacerbations and cannot be recommended as a treatment for chronic obstructive pulmonary disease, bisoprolol was safe for patients with chronic obstructive pulmonary disease. This important finding means that bisoprolol can be used to treat cardiovascular diseases in patients who have chronic obstructive pulmonary disease.
Author(s): Devereux G, Cotton S, Nath M, McMeekin N, Campbell K, Chaudhuri R, Choudhury G, De Soyza A, Fielding S, Gompertz S, Haughney J, Lee A, MacLennan G, Morice A, Norrie J, Price D, Short P, Vestbo J, Walker P, Wedzicha J, Wilson A, Wu O, Lipworth B
Publication type: Article
Publication status: Published
Journal: Health Technology Assessment
Year: 2025
Volume: 29
Issue: 17
Pages: 1-97
Print publication date: 01/05/2025
Online publication date: 01/05/2025
Acceptance date: 02/04/2018
Date deposited: 03/06/2025
ISSN (electronic): 2046-4924
Publisher: NIHR Journals Library
URL: https://doi.org/10.3310/TNDG8641
DOI: 10.3310/TNDG8641
PubMed id: 40386836
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