Chest
Volume 141, Issue 1, January 2012, Pages 81-86
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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 COPD

https://doi.org/10.1378/chest.11-0038Get rights and content

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.

Section snippets

Materials and Methods

The National Health Service (NHS) Tayside Respiratory Disease Information System (TARDIS) was used to identify patients from January 2001 to January 2010 who had a documented diagnosis history of COPD. TARDIS was developed in 2001 to support primary-care practitioners and secondary-care pulmonologists in managing patients with COPD in Tayside, Scotland. Entry into TARDIS requires a diagnosis of COPD based on GOLD guidelines,1 comprising patient demographics, respiratory symptoms, lung function,

Results

A total of 2,853 patients with COPD were included in the study, of whom 1,857 were given ICS + LABA + Tio and 996 were given ICS + LABA. Mean ± SD FEV1 % predicted at study entry was 50.8% ± 17.1% and 62.7% ± 18.9%, respectively. Mean follow-up was 4.65 years (Table 1). The group receiving triple therapy, as expected, was more severe in terms of having a lower FEV1 % and oxygen saturation as measured by pulse oximetry but were otherwise closely matched. Of the patients within the ICS + LABA +

Discussion

To our knowledge, we have conducted the first retrospective cohort study directly comparing the additive benefits of tiotropium to combination therapy with ICSs and LABAs. We have shown by means of Cox regression and considering influential covariates that the addition of tiotropium has beneficial effects on all-cause mortality and mortality due to respiratory disease. Our understanding of COPD pharmacotherapy and its benefits stems from large clinical trials and various subgroup analyses.4, 6,

Acknowledgments

Author contributions: Dr B. J. Lipworth had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Short: contributed to the study concept and design; data acquisition, analysis, and interpretation; and drafting of the submitted manuscript, critical review for important intellectual content, and approval of the final version to be published.

Dr Williamson: contributed to the study concept and design; data

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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).

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