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Original Research: COPD |

The Impact of Tiotropium on Mortality and Exacerbations When Added to Inhaled Corticosteroids and Long-Acting β-Agonist Therapy in COPDThe Impact of Tiotropium on COPD

Philip M. Short, MBChB; Peter A. Williamson, MBChB; Douglas H. J. Elder, MBChB; Samuel I. W. Lipworth, BSc; Stuart Schembri, MD; Brian J. Lipworth, MD
Author and Funding Information

From the Asthma and Allergy Research Group (Drs Short, Williamson, and B. J. Lipworth), Centre for Cardiovascular and Lung Biology (Dr Elder), Division of Medical Sciences, University of Dundee, Dundee; Bute Medical School (Mr S. I. W. Lipworth), University of St. Andrews, St. Andrews; and Department of Respiratory Medicine (Dr Schembri), Perth Royal Infirmary, Perth, Scotland.

Correspondence to: Brian J. Lipworth, MD, Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, University of Dundee, Dundee, DD1 9SY, Scotland; e-mail: brianlipworth@gmail.com


Funding/Support: This study was supported by the University of Dundee.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(1):81-86. doi:10.1378/chest.11-0038
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Background:  Tiotropium has been shown to improve lung function, quality of life, and exacerbations and reduce mortality when compared with placebo in COPD. It remains unclear whether benefits are seen when tiotropium is used in conjunction with inhaled corticosteroids (ICSs) plus long-acting β-agonists (LABAs).

Methods:  We performed a retrospective cohort study using a National Health Service database of patients with COPD in Tayside, Scotland, between 2001 and 2010 that is linked with databases regarding hospital admissions, pharmacy prescriptions, and death registries. The impact of the addition of tiotropium (Tio) to ICS + LABA therapy on all-cause mortality, hospital admissions for respiratory disease, and emergency oral corticosteroid bursts was evaluated. Adjusted hazard ratios (HRs) were calculated by Cox regression after inclusion of the following covariates: cardiovascular and respiratory disease, diabetes, smoking, age, sex, and deprivation index.

Results:  A total of 1,857 patients were given ICS + LABA + Tio, and 996 were given ICS + LABA. Mean follow-up was 4.65 years. The adjusted HR for all-cause mortality for ICS + LABA + Tio vs ICS + LABA was 0.65 (95% CI, 0.57-0.75; P < .001). Adjusted HRs for hospital admissions and oral corticosteroid bursts were 0.85 (95% CI, 0.73-0.99; P = .04) and 0.71 (95% CI, 0.63-0.80; P < .001), respectively.

Conclusions:  The study suggests that the addition of tiotropium to ICSs and LABA therapy may confer benefits in reducing all-cause mortality, hospital admissions, and oral corticosteroid bursts in patients with COPD. Triple therapy is widely used in the real-life management of COPD, with only limited scientific support. The study supports the use of triple therapy in COPD and provides a platform for randomized controlled trials specifically addressing this topic.

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