{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T18:04:21Z","timestamp":1783533861768,"version":"3.55.0"},"reference-count":122,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["15\/130\/20"],"award-info":[{"award-number":["15\/130\/20"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-2\"><jats:title>Objective(s)<\/jats:title>\n<jats:p>To determine the clinical and cost-effectiveness of adding bisoprolol (maximal dose 5\u00a0mg once daily) to usual chronic obstructive pulmonary disease therapies in patients with chronic obstructive pulmonary disease at high risk of exacerbation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title>\n<jats:p>A multicentre, pragmatic, double-blind, randomised, placebo-controlled clinical trial.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title>\n<jats:p>Seventy-six United Kingdom primary and secondary care sites.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title>\n<jats:p>People aged \u2265\u200540 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title>\n<jats:p>Participants were randomised (1\u2005:\u20051) 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\u00a0mg, 2.5\u00a0mg, 3.75\u00a0mg, 5\u00a0mg once daily).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-7\"><jats:title>Primary outcome<\/jats:title>\n<jats:p>A number of participant-reported exacerbations during the 1-year treatment period.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title>\n<jats:p>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), <jats:italic>p<\/jats:italic>\u2005=\u20050.72. 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 (\u00a3636, 95% confidence interval \u00a3118 to \u00a31391) and fewer quality-adjusted life-years (0.035, 95% confidence interval 0.059 to 0.010) compared to placebo.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-9\"><jats:title>Limitations<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-10\"><jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-11\"><jats:title>Future work<\/jats:title>\n<jats:p>To incorporate definitive statements into appropriate clinical guidelines about the safety of bisoprolol for cardiovascular indications in people with chronic obstructive pulmonary disease.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-12\"><jats:title>Trial registration<\/jats:title>\n<jats:p>This trial is registered as ISRCTN10497306.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-13\"><jats:title>Funding<\/jats:title>\n<jats:p>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 <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 29, No. 17. See the NIHR Funding and Awards website for further award information.<\/jats:p>\n<\/jats:sec>","DOI":"10.3310\/tndg8641","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T10:10:32Z","timestamp":1747649432000},"page":"1-97","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Bisoprolol for patients with chronic obstructive pulmonary disease at high risk of exacerbation: the BICS RCT"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0024-4887","authenticated-orcid":true,"given":"Graham","family":"Devereux","sequence":"first","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7883-0608","authenticated-orcid":true,"given":"Seonaidh","family":"Cotton","sequence":"additional","affiliation":[{"name":"Centre for Healthcare Randomised Trials (CHaRT), 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