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      Statin Use and the Risk of Subsequent Hospitalized Exacerbations in COPD Patients with Frequent Exacerbations

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          Abstract

          Rationale

          The potential benefits of statins for the prevention of exacerbations in patients with COPD remains controversial. No previous studies have investigated the impact of statins on clinical outcomes in COPD patients with frequent exacerbations.

          Objective

          This study aimed to evaluate the association between the use of statins and the risk of subsequent hospitalized exacerbations in COPD frequent exacerbators.

          Materials and Methods

          We conducted a population-based cohort study using the Taiwan National Health Insurance Research Database. 139,223 COPD patients with a first hospitalized exacerbation between 2004 and 2012 were analyzed. Among them, 35,482 had a second hospitalized exacerbation within a year after the first exacerbation, and were defined as frequent exacerbators. 1:4 propensity score matching was used to create matched samples of statin users and non-users. The competing risk regression analysis model was used to evaluate the association between statin use and exacerbation risk.

          Results

          The use of statins was associated with a significantly reduced risk in subsequent hospitalized exacerbations in COPD patients after their first hospitalized exacerbation (adjusted subdistribution hazard ration [SHR], 0.89; 95% CI, 0.85–0.93, P<0.001). In frequent exacerbators, the SHR for subsequent hospitalized exacerbations in statins users was 0.88 (95% CI, 0.81–0.94, P=0.001). Subgroup analysis among frequent exacerbators demonstrated that the use of statins only provided a protective effect against subsequent hospitalized exacerbations in male patients aged 75 years and older, with coexisting diabetes mellitus, hypertension or cardiovascular disease, and no protective effect was observed in those with lung cancer or depression. Current use of statins was associated with a greater protective effect for reducing subsequent hospitalized exacerbation.

          Conclusion

          The use of statins was associated with a significant reduction in the risk of hospitalized exacerbations in COPD patients after a first hospitalized exacerbation and in specified COPD frequent exacerbators.

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          Most cited references 24

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          From COPD to chronic systemic inflammatory syndrome?

           L. Fabbri,  K. F. Rabe (2007)
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            Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease.

            There is a need to identify clinically meaningful predictors of mortality following hospitalized COPD exacerbation. The aim of this study was to systematically review the literature to identify clinically important factors that predict mortality after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD). Eligible studies considered adults admitted to hospital with COPD exacerbation. Two authors independently abstracted data. Odds ratios were then calculated by comparing the prevalence of each predictor in survivors versus nonsurvivors. For continuous variables, mean differences were pooled by the inverse of their variance, using a random effects model. There were 37 studies included (189,772 study subjects) with risk of death ranging from 3.6% for studies considering short-term mortality, 31.0% for long-term mortality (up to 2 yr after hospitalization), and 29.0% for studies that considered solely intensive care unit (ICU)-admitted study subjects. Twelve prognostic factors (age, male sex, low body mass index, cardiac failure, chronic renal failure, confusion, long-term oxygen therapy, lower limb edema, Global Initiative for Chronic Lung Disease criteria stage 4, cor pulmonale, acidemia, and elevated plasma troponin level) were significantly associated with increased short-term mortality. Nine prognostic factors (age, low body mass index, cardiac failure, diabetes mellitus, ischemic heart disease, malignancy, FEV1, long-term oxygen therapy, and PaO2 on admission) were significantly associated with long-term mortality. Three factors (age, low Glasgow Coma Scale score, and pH) were significantly associated with increased risk of mortality in ICU-admitted study subjects. Different factors correlate with mortality from COPD exacerbation in the short term, long term, and after ICU admission. These parameters may be useful to develop tools for prediction of outcome in clinical practice.
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              Simvastatin for the prevention of exacerbations in moderate-to-severe COPD.

              Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial. We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome. Patients were eligible if they were 40 to 80 years of age, had COPD (defined by a forced expiratory volume in 1 second [FEV1] of less than 80% and a ratio of FEV1 to forced vital capacity of less than 70%), and had a smoking history of 10 or more pack-years, were receiving supplemental oxygen or treatment with glucocorticoids or antibiotic agents, or had had an emergency department visit or hospitalization for COPD within the past year. Patients with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers. A total of 885 participants with COPD were enrolled for approximately 641 days; 44% of the patients were women. The patients had a mean (±SD) age of 62.2±8.4 years, an FEV1 that was 41.6±17.7% of the predicted value, and a smoking history of 50.6±27.4 pack-years. At the time of study closeout, the low-density lipoprotein cholesterol levels were lower in the simvastatin-treated patients than in those who received placebo. The mean number of exacerbations per person-year was similar in the simvastatin and placebo groups: 1.36±1.61 exacerbations and 1.39±1.73 exacerbations, respectively (P=0.54). The median number of days to the first exacerbation was also similar: 223 days (95% confidence interval [CI], 195 to 275) and 231 days (95% CI, 193 to 303), respectively (P=0.34). The number of nonfatal serious adverse events per person-year was similar, as well: 0.63 events with simvastatin and 0.62 events with placebo. There were 30 deaths in the placebo group and 28 in the simvastatin group (P=0.89). Simvastatin at a daily dose of 40 mg did not affect exacerbation rates or the time to a first exacerbation in patients with COPD who were at high risk for exacerbations. (Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671.).
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                COPD
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                10 February 2020
                2020
                : 15
                : 289-299
                Affiliations
                [1 ]Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung Medical Foundation , Chiayi, Taiwan
                [2 ]Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University , Taoyuan City, Taiwan
                [3 ]Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung Medical Foundation , Chiayi, Taiwan
                [4 ]Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chang Gung Medical Foundation , Chiayi, Taiwan
                [5 ]School of Traditional Chinese Medicine, College of Medicine, Chang Gung University , Taoyuan, Taiwan
                [6 ]Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation , Taoyuan, Taiwan
                [7 ]Department of Respiratory Therapy, School of Medicine, Chang Gung University , Taoyuan, Taiwan
                [8 ]Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health , Taipei, Taiwan
                [9 ]Department of Public Health, National Taiwan University College of Public Health , Taipei, Taiwan
                [10 ]Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine , Taipei, Taiwan
                [11 ]Office of Occupational Safety and Health, National Taiwan University Hospital , Taipei, Taiwan
                [12 ]Department of Radiation Oncology, Chiayi Chang Gung Memorial Hospital, Chang Gung Medical Foundation , Chiayi, Taiwan
                Author notes
                Correspondence: Meng-Jer Hsieh Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung Medical Foundation , No. 6, West Sec., Jiapu Road, Puzi City, Chiayi County61363, TaiwanTel +886-5-3621000 Email mengjer@yahoo.com
                Article
                229047
                10.2147/COPD.S229047
                7020922
                © 2020 Lin 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 2, Tables: 4, References: 35, Pages: 11
                Funding
                This study was supported by a grant from Chiayi Chang Gung Memorial Hospital, Taiwan (grant no. CORPG6D0211).
                Categories
                Original Research

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