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Published in: Lung 5/2014

01-10-2014

Impact of Long-Acting Bronchodilators and Exposure to Inhaled Corticosteroids on Mortality in COPD: A Real-Life Retrospective Cohort Study

Authors: Arvind Manoharan, Phillip M. Short, William J. Anderson, Brian J. Lipworth

Published in: Lung | Issue 5/2014

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Abstract

Introduction

We performed a real-life retrospective analysis to assess the impact of long-acting bronchodilator therapy and associated exposure to inhaled corticosteroids (ICS) on all-cause and cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD).

Methods

We used record linkage data from patients with a diagnosis of COPD in Tayside, Scotland, between 2001 and 2010. All-cause and cardiovascular mortality were assessed using Cox proportional hazard regression.

Results

A total of 4,133 patients were included, mean FEV1 of 59.5 %, mean age of 68.9 years and mean follow-up of 4.6 years. There were 623 who were exposed to long-acting bronchodilators only and 3,510 to long-acting bronchodilators plus ICS. 1,372 patients (33 %) died during the study period. Compared with controls taking only long-acting bronchodilators either alone or in combination, all-cause mortality was reduced in patients taking long-acting muscarinic antagonist (LAMA) + ICS as dual therapy: adjusted hazard ratio 0.62 (95 % CI 0.45–0.85), but not by long-acting beta-agonist (LABA) + ICS: adjusted hazard ratio 1.02 (95 % CI 0.80–1.31). Cardiovascular mortality was not reduced by dual therapy with either LABA or LAMA and concomitant ICS exposure. All-cause and cardiovascular mortality were both reduced in patients taking triple therapy with LABA + LAMA + ICS: adjusted hazard ratio 0.51 (95 % CI 0.41–0.64) and 0.56 (95 % CI 0.35–0.90), respectively.

Conclusion

In patients exposed to ICS, concomitant use of LAMA alone as dual therapy or in combination with LABA as triple therapy were associated with reductions in all-cause mortality, while concomitant use of LABA without LAMA conferred no reduction. Moreover, only triple therapy was found to confer benefits on cardiovascular mortality.
Literature
1.
go back to reference National Institute for Health and Clinical Excellence (2010) Chronic obstructive pulmonary disease. NICE guideline (update) consultation. National Institute for Health and Clinical Excellence, London National Institute for Health and Clinical Excellence (2010) Chronic obstructive pulmonary disease. NICE guideline (update) consultation. National Institute for Health and Clinical Excellence, London
2.
go back to reference Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW et al (2007) Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 356:775–789CrossRefPubMed Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW et al (2007) Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 356:775–789CrossRefPubMed
3.
go back to reference Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S et al (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359:1543–1554CrossRefPubMed Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S et al (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359:1543–1554CrossRefPubMed
4.
go back to reference Salpeter SR, Ormiston TM, Salpeter EE (2004) Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest 125:2309–2321CrossRefPubMed Salpeter SR, Ormiston TM, Salpeter EE (2004) Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest 125:2309–2321CrossRefPubMed
5.
go back to reference Singh S, Loke YK, Enright P, Furberg CD (2013) Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications. Thorax 68:114–116CrossRefPubMed Singh S, Loke YK, Enright P, Furberg CD (2013) Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications. Thorax 68:114–116CrossRefPubMed
6.
go back to reference Beasley R, Singh S, Loke YK, Enright P, Furberg CD (2012) Call for worldwide withdrawal of tiotropium Respimat mist inhaler. BMJ 345:e7390CrossRefPubMed Beasley R, Singh S, Loke YK, Enright P, Furberg CD (2012) Call for worldwide withdrawal of tiotropium Respimat mist inhaler. BMJ 345:e7390CrossRefPubMed
7.
go back to reference Hohlfeld J, Sharma A, van Noord J et al (2014) Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol 54(4):405–414. doi:10.1002/jcph.215 CrossRefPubMed Hohlfeld J, Sharma A, van Noord J et al (2014) Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol 54(4):405–414. doi:10.​1002/​jcph.​215 CrossRefPubMed
8.
go back to reference Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B et al (2013) Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med 369:1491–1501CrossRefPubMed Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B et al (2013) Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med 369:1491–1501CrossRefPubMed
9.
go back to reference Short PM, Williamson PA, Elder DH, Lipworth SI, Schembri S, Lipworth BJ (2012) The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting beta-agonist therapy in COPD. Chest 141:81–86CrossRefPubMed Short PM, Williamson PA, Elder DH, Lipworth SI, Schembri S, Lipworth BJ (2012) The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting beta-agonist therapy in COPD. Chest 141:81–86CrossRefPubMed
10.
go back to reference Janson C, Larsson K, Lisspers KH, Ställberg B, Stratelis G, Goike H et al (2013) Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting beta2 agonist: observational matched cohort study (PATHOS). BMJ 346:f3306PubMedCentralCrossRefPubMed Janson C, Larsson K, Lisspers KH, Ställberg B, Stratelis G, Goike H et al (2013) Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting beta2 agonist: observational matched cohort study (PATHOS). BMJ 346:f3306PubMedCentralCrossRefPubMed
11.
go back to reference Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB (2008) Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med 149:380–390CrossRefPubMed Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB (2008) Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med 149:380–390CrossRefPubMed
12.
go back to reference Gershon A, Croxford R, Calzavara A, To T, Stanbrook MB, Upshur R et al (2013) Cardiovascular safety of inhaled long-acting bronchodilators in individuals with chronic obstructive pulmonary disease long-acting bronchodilators in COPD long-acting bronchodilators in COPD. JAMA Intern Med 173:1175–1185CrossRefPubMed Gershon A, Croxford R, Calzavara A, To T, Stanbrook MB, Upshur R et al (2013) Cardiovascular safety of inhaled long-acting bronchodilators in individuals with chronic obstructive pulmonary disease long-acting bronchodilators in COPD long-acting bronchodilators in COPD. JAMA Intern Med 173:1175–1185CrossRefPubMed
13.
go back to reference Lee TA, Wilke C, Joo M, Stroupe KT, Krishnan JA, Schumock GT et al (2009) Outcomes associated with tiotropium use in patients with chronic obstructive pulmonary disease. Arch Intern Med 169:1403–1410CrossRefPubMed Lee TA, Wilke C, Joo M, Stroupe KT, Krishnan JA, Schumock GT et al (2009) Outcomes associated with tiotropium use in patients with chronic obstructive pulmonary disease. Arch Intern Med 169:1403–1410CrossRefPubMed
14.
go back to reference Dong YH, Lin HH, Shau WY, Wu YC, Chang CH, Lai MS (2013) Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials. Thorax 68:48–56CrossRefPubMed Dong YH, Lin HH, Shau WY, Wu YC, Chang CH, Lai MS (2013) Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials. Thorax 68:48–56CrossRefPubMed
Metadata
Title
Impact of Long-Acting Bronchodilators and Exposure to Inhaled Corticosteroids on Mortality in COPD: A Real-Life Retrospective Cohort Study
Authors
Arvind Manoharan
Phillip M. Short
William J. Anderson
Brian J. Lipworth
Publication date
01-10-2014
Publisher
Springer US
Published in
Lung / Issue 5/2014
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-014-9611-8

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