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      Impact of selective and nonselective beta-blockers on the risk of severe exacerbations in patients with COPD

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          Abstract

          Background

          There is conflicting information regarding the effects of selective and nonselective beta-blocker treatment in patients with COPD.

          Participants and methods

          This nested case–control study used the Taiwan National Health Insurance Research Database. We included COPD patients who used inhalation steroid and beta-blockers between 1998 and 2010. From this cohort, there were 16,067 patients with severe exacerbations included in the analysis and 55,970 controls matched on age, sex, COPD diagnosis year, and beta-blockers treatment duration by risk set sampling.

          Results

          For the selective beta-blocker users, the current users had a lower risk of severe exacerbations than the nonusers (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.85–0.96). In contrast, for the nonselective beta-blocker users, the current users had a higher risk of severe acute exacerbations than the nonusers (OR, 1.21; 95% CI, 1.14–1.27). A higher risk of severe exacerbation during increasing mean daily dose or within about the initial 300 days was found in nonselective beta-blockers, but not in selective beta-blockers. One selective beta-blocker, betaxolol, had a significantly lower risk of severe exacerbations (OR, 0.75; 95% CI, 0.60–0.95). Two nonselective beta-blockers (labetalol and propranolol) were associated with a significantly higher risk of exacerbations (OR, 1.49; 95% CI, 1.32–1.67 for labetalol; OR, 1.16; 95% CI, 1.10–1.23 for propranolol).

          Conclusion

          Selective beta-blockers can be cautiously prescribed for patients with COPD and cardiovascular disease (CVD), however, nonselective beta-blockers should not be prescribed for patients with COPD. Betaxolol may be the preferred choice of suitable selective beta-blocker for patients with COPD, however, labetalol and propranolol should be avoided for patients with COPD.

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          Most cited references 17

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          Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction.

          Long-term administration of beta-adrenergic blockers to patients after myocardial infarction improves survival. However, physicians are reluctant to administer beta-blockers to many patients, such as older patients and those with chronic pulmonary disease, left ventricular dysfunction, or non-Q-wave myocardial infarction. The medical records of 201,752 patients with myocardial infarction were abstracted by the Cooperative Cardiovascular Project, which was sponsored by the Health Care Financing Administration. Using a Cox proportional-hazards model that accounted for multiple factors that might influence survival, we compared mortality among patients treated with beta-blockers with mortality among untreated patients during the two years after myocardial infarction. A total of 34 percent of the patients received beta-blockers. The percentage was lower among the very elderly, blacks, and patients with the lowest ejection fractions, heart failure, chronic obstructive pulmonary disease, elevated serum creatinine concentrations, or type 1 diabetes mellitus. Nevertheless, mortality was lower in every subgroup of patients treated with beta-blockade than in untreated patients. In patients with myocardial infarction and no other complications, treatment with beta-blockers was associated with a 40 percent reduction in mortality. Mortality was also reduced by 40 percent in patients with non-Q-wave infarction and those with chronic obstructive pulmonary disease. Blacks, patients 80 years old or older, and those with a left ventricular ejection fraction below 20 percent, serum creatinine concentration greater than 1.4 mg per deciliter (124 micromol per liter), or diabetes mellitus had a lower percentage reduction in mortality. Given, however, the higher mortality rates in these subgroups, the absolute reduction in mortality was similar to or greater than that among patients with no specific risk factors. After myocardial infarction, patients with conditions that are often considered contraindications to beta-blockade (such as heart failure, pulmonary disease, and older age) and those with nontransmural infarction benefit from beta-blocker therapy.
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            Effect of β blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study

            Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD. Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry. Setting Tayside, Scotland (2001–2010) Population 5977 patients aged >50 years with a diagnosis of COPD. Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates. Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective. There was a 22% overall reduction in all cause mortality with β blocker use. Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD. Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker. There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function.
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              Beta-Blockers Reduced the Risk of Mortality and Exacerbation in Patients with COPD: A Meta-Analysis of Observational Studies

              Background Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD). Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases. But the effects of beta-blockers on outcomes in patients with COPD remain controversial. The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD. Methods An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD. The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD. Results Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included. The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD. The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71). In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54–0.76) and 0.74 (0.58–0.93), respectively. Conclusion The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD. Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2017
                11 October 2017
                : 12
                : 2987-2996
                Affiliations
                [1 ]Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City
                [2 ]Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan
                [3 ]Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City
                [4 ]Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei
                [5 ]Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
                Author notes
                Correspondence: Cheng-Yi Wang, Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu-Jen Catholic University, 510, Zhongzheng Road, Xinzhuang District, New Taipei City 23148, Taiwan, Tel +886 2 2219 3391 ext 15433, Fax +886 2 2 2219 0651, Email cywang@ 123456mospital.com
                Hao-Chien Wang, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 10041, Taiwan, Tel +886 2 2356 2905, Fax +886 2 2358 2867, Email haochienwang@ 123456gmail.com
                Article
                copd-12-2987
                10.2147/COPD.S145913
                5644571
                © 2017 Huang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                beta-blocker, copd, selective, nonselective

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