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      Beta-blockers reduce severe exacerbation in patients with mild chronic obstructive pulmonary disease with atrial fibrillation: a population-based cohort study

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          Abstract

          Background and objective

          Beta-blockers (BBs) decrease mortality and acute exacerbation (AE) rates in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease; however, information on their effects in patients with COPD and atrial fibrillation (AF) is limited. We aimed to assess the AE risk in patients with different severities of COPD and AF receiving BBs compared with that in patients receiving calcium channel blockers (CCBs).

          Methods

          This retrospective cohort study used data from the Taiwan National Health Insurance Database from 2009 to 2018. Outcomes included AE-related emergency room visits and hospitalisation. HRs and 95% CIs were estimated using the Cox proportional hazards model. COPD severity was classified as mild or severe based on exacerbation history. Sensitivity analyses included treatment and subgroup analyses, and competing risk adjustment.

          Results

          After propensity score matching, 4486 pairs of BB and CCB users from 13 462 eligible patients were included. The exacerbation risk for BB users was lower (HR 0.80; 95% CI 0.72 to 0.89) than that of CCB users. After stratification, BB benefits persisted in the mild COPD group (HR 0.75; 95% CI 0.66 to 0.85), unlike the severe COPD group (HR 0.95; 95% CI 0.75 to 1.20). The results of the subgroup analysis showed consistent protective effects even in patients without heart failure or myocardial infarction (adjusted HR 0.82; 95% CI 0.71 to 0.94).

          Conclusion

          We found that BB use in patients with mild COPD and AF was associated with a lower exacerbation risk than CCB use, and that close monitoring of BB use in patients with severe COPD and AF is warranted.

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          Most cited references31

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            Susceptibility to exacerbation in chronic obstructive pulmonary disease.

            John R. Hurst, Jørgen Vestbo, Antonio Anzueto … (2010)
            Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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              Taiwan’s National Health Insurance Research Database: past and future

              Cheng-Yang Hsieh, Chien-Chou Su, Shih-Chieh Shao … (2019)
              Abstract Taiwan’s National Health Insurance Research Database (NHIRD) exemplifies a population-level data source for generating real-world evidence to support clinical decisions and health care policy-making. Like with all claims databases, there have been some validity concerns of studies using the NHIRD, such as the accuracy of diagnosis codes and issues around unmeasured confounders. Endeavors to validate diagnosed codes or to develop methodologic approaches to address unmeasured confounders have largely increased the reliability of NHIRD studies. Recently, Taiwan’s Ministry of Health and Welfare (MOHW) established a Health and Welfare Data Center (HWDC), a data repository site that centralizes the NHIRD and about 70 other health-related databases for data management and analyses. To strengthen the protection of data privacy, investigators are required to conduct on-site analysis at an HWDC through remote connection to MOHW servers. Although the tight regulation of this on-site analysis has led to inconvenience for analysts and has increased time and costs required for research, the HWDC has created opportunities for enriched dimensions of study by linking across the NHIRD and other databases. In the near future, researchers will have greater opportunity to distill knowledge from the NHIRD linked to hospital-based electronic medical records databases containing unstructured patient-level information by using artificial intelligence techniques, including machine learning and natural language processes. We believe that NHIRD with multiple data sources could represent a powerful research engine with enriched dimensions and could serve as a guiding light for real-world evidence-based medicine in Taiwan.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open Respir Res
                Journal ID (iso-abbrev): BMJ Open Respir Res
                Journal ID (hwp): bmjresp
                Journal ID (publisher-id): bmjopenrespres
                Title: BMJ Open Respiratory Research
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2052-4439
                Publication date Collection: 2023
                Publication date (Electronic): 20 November 2023
                Volume: 10
                Issue: 1
                Electronic Location Identifier: e001854
                Affiliations
                [1 ]departmentSchool of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences , Ringgold_34912National Cheng Kung University , Tainan, Taiwan
                [2 ]departmentDepartment of Internal Medicine , Ringgold_34912National Cheng Kung University , Tainan, Taiwan
                [3 ]departmentInstitute of clinical medicine , National Cheng Kung University , Tainan, Taiwan
                [4 ]departmentDepartment of Pharmacy , Ringgold_38024Kaohsiung Veterans General Hospital , Kaohsiung, Taiwan
                [5 ]departmentHealth Outcome Research Center , National Cheng Kung University , Tainan, Taiwan
                [6 ]departmentDepartment of Pharmacy , Ringgold_63461National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University , Tainan, Taiwan
                Author notes
                [Correspondence to ] Ching-Lan Cheng; clcheng@ 123456mail.ncku.edu.tw
                Author information
                http://orcid.org/0000-0001-9258-3239
                Article
                Publisher ID: bmjresp-2023-001854
                DOI: 10.1136/bmjresp-2023-001854
                PMC ID: 10660430
                PubMed ID: 37989489
                SO-VID: 446b69a6-5388-4baa-8d2f-7c663627c7bc
                Copyright © © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
                License:

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Date received : 30 May 2023
                Date accepted : 27 October 2023
                Categories
                Subject: Chronic Obstructive Pulmonary Disease
                Subject: 1506
                Subject: 2215
                Custom metadata
                special-feature unlocked

                Keywords: copd exacerbations,clinical epidemiology
                Data availability:
                Keywords: copd exacerbations, clinical epidemiology

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