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Published in: Respiratory Research 1/2009

Open Access 01-12-2009 | Research

Impact of statins and ACE inhibitors on mortality after COPD exacerbations

Authors: Eric M Mortensen, Laurel A Copeland, Mary Jo V Pugh, Marcos I Restrepo, Rosa Malo de Molina, Brandy Nakashima, Antonio Anzueto

Published in: Respiratory Research | Issue 1/2009

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Abstract

Background

The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.

Methods

We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.

Results

We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.

Conclusion

Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.
Literature
1.
go back to reference Anonymous: Health, United States, 2004 With chartbook on trends in the health of Americans. Hyattsville, Maryland: National Center for Health Statistics; 2004. Anonymous: Health, United States, 2004 With chartbook on trends in the health of Americans. Hyattsville, Maryland: National Center for Health Statistics; 2004.
2.
go back to reference Pauwels RA, Buist AS, Ma P, Jenkins CR, Hurd SS: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): executive summary. Respir Care 2001,46(8):798–825.PubMed Pauwels RA, Buist AS, Ma P, Jenkins CR, Hurd SS: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): executive summary. Respir Care 2001,46(8):798–825.PubMed
3.
go back to reference Celli BR, MacNee W: Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004,23(6):932–946.CrossRefPubMed Celli BR, MacNee W: Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004,23(6):932–946.CrossRefPubMed
4.
go back to reference Yoshida T, Tuder RM: Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease. Physiol Rev 2007,87(3):1047–1082.CrossRefPubMed Yoshida T, Tuder RM: Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease. Physiol Rev 2007,87(3):1047–1082.CrossRefPubMed
5.
6.
go back to reference Yende S, Tuomanen EI, Wunderink R, Kanaya A, Newman AB, Harris T, de Rekeneire N, Kritchevsky SB: Preinfection systemic inflammatory markers and risk of hospitalization due to pneumonia. Am J Respir Crit Care Med 2005,172(11):1440–1446.CrossRefPubMedPubMedCentral Yende S, Tuomanen EI, Wunderink R, Kanaya A, Newman AB, Harris T, de Rekeneire N, Kritchevsky SB: Preinfection systemic inflammatory markers and risk of hospitalization due to pneumonia. Am J Respir Crit Care Med 2005,172(11):1440–1446.CrossRefPubMedPubMedCentral
7.
go back to reference Keatings VM, Cave SJ, Henry MJ, Morgan K, O'Connor CM, FitzGerald MX, Kalsheker N: A polymorphism in the tumor necrosis factor-alpha gene promoter region may predispose to a poor prognosis in COPD. Chest 2000,118(4):971–975.CrossRefPubMed Keatings VM, Cave SJ, Henry MJ, Morgan K, O'Connor CM, FitzGerald MX, Kalsheker N: A polymorphism in the tumor necrosis factor-alpha gene promoter region may predispose to a poor prognosis in COPD. Chest 2000,118(4):971–975.CrossRefPubMed
8.
go back to reference Banerjee D, Khair OA, Honeybourne D: Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD. Eur Respir J 2004,23(5):685–691.CrossRefPubMed Banerjee D, Khair OA, Honeybourne D: Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD. Eur Respir J 2004,23(5):685–691.CrossRefPubMed
9.
go back to reference Sethi S, Muscarella K, Evans N, Klingman KL, Grant BJ, Murphy TF: Airway inflammation and etiology of acute exacerbations of chronic bronchitis. Chest 2000,118(6):1557–1565.CrossRefPubMed Sethi S, Muscarella K, Evans N, Klingman KL, Grant BJ, Murphy TF: Airway inflammation and etiology of acute exacerbations of chronic bronchitis. Chest 2000,118(6):1557–1565.CrossRefPubMed
10.
11.
go back to reference Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S: Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001,103(15):1933–1935.CrossRefPubMed Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S: Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001,103(15):1933–1935.CrossRefPubMed
12.
go back to reference Strandberg TE, Vanhanen H, Tikkanen MJ: Effect of statins on C-reactive protein in patients with coronary artery disease. Lancet 1999,353(9147):118–119.CrossRefPubMed Strandberg TE, Vanhanen H, Tikkanen MJ: Effect of statins on C-reactive protein in patients with coronary artery disease. Lancet 1999,353(9147):118–119.CrossRefPubMed
13.
go back to reference Gullestad L, Aukrust P, Ueland T, Espevik T, Yee G, Vagelos R, Froland SS, Fowler M: Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure. Journal of the American College of Cardiology 1999,34(7):2061–2067.CrossRefPubMed Gullestad L, Aukrust P, Ueland T, Espevik T, Yee G, Vagelos R, Froland SS, Fowler M: Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure. Journal of the American College of Cardiology 1999,34(7):2061–2067.CrossRefPubMed
14.
go back to reference Alkharfy KM, Kellum JA, Matzke GR: Unintended immunomodulation: part II. Effects of pharmacological agents on cytokine activity. Shock 2000,13(5):346–360.CrossRefPubMed Alkharfy KM, Kellum JA, Matzke GR: Unintended immunomodulation: part II. Effects of pharmacological agents on cytokine activity. Shock 2000,13(5):346–360.CrossRefPubMed
15.
go back to reference Skerrett SJ, Park DR: Anti-inflammatory treatment of acute and chronic pneumonia. Seminars in Respiratory Infections 2001,16(1):76–84.CrossRefPubMed Skerrett SJ, Park DR: Anti-inflammatory treatment of acute and chronic pneumonia. Seminars in Respiratory Infections 2001,16(1):76–84.CrossRefPubMed
16.
go back to reference Frost FJ, Petersen H, Tollestrup K, Skipper B: Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest 2007,131(4):1006–1012.CrossRefPubMed Frost FJ, Petersen H, Tollestrup K, Skipper B: Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest 2007,131(4):1006–1012.CrossRefPubMed
17.
go back to reference Mancini GB, Etminan M, Zhang B, Levesque LE, FitzGerald JM, Brophy JM: Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 2006,47(12):2554–2560.CrossRefPubMed Mancini GB, Etminan M, Zhang B, Levesque LE, FitzGerald JM, Brophy JM: Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 2006,47(12):2554–2560.CrossRefPubMed
18.
go back to reference Soyseth V, Brekke PH, Smith P, Omland T: Statin use is associated with reduced mortality in COPD. Eur Respir J 2007,29(2):279–283.CrossRefPubMed Soyseth V, Brekke PH, Smith P, Omland T: Statin use is associated with reduced mortality in COPD. Eur Respir J 2007,29(2):279–283.CrossRefPubMed
19.
go back to reference Blamoun AI, Batty GN, DeBari VA, Rashid AO, Sheikh M, Khan MA: Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study. International Journal of Clinical Practice 2008, 62:1373–1378.CrossRefPubMed Blamoun AI, Batty GN, DeBari VA, Rashid AO, Sheikh M, Khan MA: Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study. International Journal of Clinical Practice 2008, 62:1373–1378.CrossRefPubMed
20.
go back to reference Pugh MJ, Fincke BG, Bierman AS, Chang BH, Rosen AK, Cunningham FE, Amuan ME, Burk ML, Berlowitz DR: Potentially inappropriate prescribing in elderly veterans: are we using the wrong drug, wrong dose, or wrong duration? J Am Geriatr Soc 2005,53(8):1282–1289.CrossRefPubMed Pugh MJ, Fincke BG, Bierman AS, Chang BH, Rosen AK, Cunningham FE, Amuan ME, Burk ML, Berlowitz DR: Potentially inappropriate prescribing in elderly veterans: are we using the wrong drug, wrong dose, or wrong duration? J Am Geriatr Soc 2005,53(8):1282–1289.CrossRefPubMed
21.
go back to reference Joo MJ, Lee TA, Bartle B, Graaff WB, Weiss KB: Patterns of Healthcare Utilization by COPD Severity: A Pilot Study. Lung 2008,186(5):307–312.CrossRefPubMed Joo MJ, Lee TA, Bartle B, Graaff WB, Weiss KB: Patterns of Healthcare Utilization by COPD Severity: A Pilot Study. Lung 2008,186(5):307–312.CrossRefPubMed
22.
go back to reference Selim AJ, Berlowitz DR, Fincke G, Cong Z, Rogers W, Haffer SC, Ren XS, Lee A, Qian SX, Miller DR, Spiro A 3rd, Selim BJ, Kazis LE: The health status of elderly veteran enrollees in the Veterans Health Administration. J Am Geriatr Soc 2004,52(8):1271–1276.CrossRefPubMed Selim AJ, Berlowitz DR, Fincke G, Cong Z, Rogers W, Haffer SC, Ren XS, Lee A, Qian SX, Miller DR, Spiro A 3rd, Selim BJ, Kazis LE: The health status of elderly veteran enrollees in the Veterans Health Administration. J Am Geriatr Soc 2004,52(8):1271–1276.CrossRefPubMed
23.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chron Dis 1987,40(5):373–383.CrossRefPubMed Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chron Dis 1987,40(5):373–383.CrossRefPubMed
24.
go back to reference Charlson M, Szatrowski TP, Peterson J, Gold J: Validation of a combined comorbidity index. J Clin Epidemiol 1994,47(11):1245–1251.CrossRefPubMed Charlson M, Szatrowski TP, Peterson J, Gold J: Validation of a combined comorbidity index. J Clin Epidemiol 1994,47(11):1245–1251.CrossRefPubMed
25.
go back to reference Hess LM, Raebel MA, Conner DA, Malone DC: Measurement of adherence in pharmacy administrative databases: a proposal for standard definitions and preferred measures. Ann Pharmacother 2006,40(7–8):1280–1288.CrossRefPubMed Hess LM, Raebel MA, Conner DA, Malone DC: Measurement of adherence in pharmacy administrative databases: a proposal for standard definitions and preferred measures. Ann Pharmacother 2006,40(7–8):1280–1288.CrossRefPubMed
26.
go back to reference Claxton AJ, Cramer J, Pierce C: A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001,23(8):1296–1310.CrossRefPubMed Claxton AJ, Cramer J, Pierce C: A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001,23(8):1296–1310.CrossRefPubMed
27.
go back to reference Schneeweiss S, Seeger JD, Maclure M, Wang PS, Avorn J, Glynn RJ: Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data. Am J Epidemiol 2001,154(9):854–864.CrossRefPubMed Schneeweiss S, Seeger JD, Maclure M, Wang PS, Avorn J, Glynn RJ: Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data. Am J Epidemiol 2001,154(9):854–864.CrossRefPubMed
28.
go back to reference Cowper DC, Kubal JD, Maynard C, Hynes DM: A primer and comparative review of major US mortality databases. Ann Epidemiol 2002,12(7):462–468.CrossRefPubMed Cowper DC, Kubal JD, Maynard C, Hynes DM: A primer and comparative review of major US mortality databases. Ann Epidemiol 2002,12(7):462–468.CrossRefPubMed
29.
go back to reference Stone RA, Obrosky DS, Singer DE, Kapoor WN, Fine MJ: Propensity score adjustment for pretreatment differences between hospitalized and ambulatory patients with community-acquired pneumonia. Pneumonia Patient Outcomes Research Team (PORT) Investigators. Med Care 1995,33(4 Suppl):AS56–66.PubMed Stone RA, Obrosky DS, Singer DE, Kapoor WN, Fine MJ: Propensity score adjustment for pretreatment differences between hospitalized and ambulatory patients with community-acquired pneumonia. Pneumonia Patient Outcomes Research Team (PORT) Investigators. Med Care 1995,33(4 Suppl):AS56–66.PubMed
30.
go back to reference Klungel OH, Martens EP, Psaty BM, Grobbee DE, Sullivan SD, Stricker BH, Leufkens HG, de Boer A: Methods to assess intended effects of drug treatment in observational studies are reviewed. J Clin Epidemiol 2004,57(12):1223–1231.CrossRefPubMed Klungel OH, Martens EP, Psaty BM, Grobbee DE, Sullivan SD, Stricker BH, Leufkens HG, de Boer A: Methods to assess intended effects of drug treatment in observational studies are reviewed. J Clin Epidemiol 2004,57(12):1223–1231.CrossRefPubMed
31.
go back to reference Rosenbaum PR, Rubin DB: The central role of the propensity score in observational studies for causal effects. Biometrika 1983, 70:41–55.CrossRef Rosenbaum PR, Rubin DB: The central role of the propensity score in observational studies for causal effects. Biometrika 1983, 70:41–55.CrossRef
32.
33.
go back to reference Grijalva CG, Arbogast PG, Griffin MR: Statins and influenza/COPD mortality. Chest 2007,132(4):1407.CrossRefPubMed Grijalva CG, Arbogast PG, Griffin MR: Statins and influenza/COPD mortality. Chest 2007,132(4):1407.CrossRefPubMed
34.
35.
go back to reference Elixhauser A, Steiner C, Harris DR, Coffey RM: Comorbidity measures for use with administrative data. Med Care 1998,36(1):8–27.CrossRefPubMed Elixhauser A, Steiner C, Harris DR, Coffey RM: Comorbidity measures for use with administrative data. Med Care 1998,36(1):8–27.CrossRefPubMed
36.
go back to reference Lee TA, Bartle B, Weiss KB: Spirometry use in clinical practice following diagnosis of COPD. Chest 2006,129(6):1509–1515.CrossRefPubMed Lee TA, Bartle B, Weiss KB: Spirometry use in clinical practice following diagnosis of COPD. Chest 2006,129(6):1509–1515.CrossRefPubMed
37.
38.
go back to reference Piette JD, Heisler M: Problems due to medication costs among VA and non-VA patients with chronic illnesses. Am J Manag Care 2004,10(11 Pt 2):861–868.PubMed Piette JD, Heisler M: Problems due to medication costs among VA and non-VA patients with chronic illnesses. Am J Manag Care 2004,10(11 Pt 2):861–868.PubMed
Metadata
Title
Impact of statins and ACE inhibitors on mortality after COPD exacerbations
Authors
Eric M Mortensen
Laurel A Copeland
Mary Jo V Pugh
Marcos I Restrepo
Rosa Malo de Molina
Brandy Nakashima
Antonio Anzueto
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2009
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-10-45

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