Tiotropium might improve survival in subjects with COPD at high risk of mortality

Respiratory Research

Marc Decramer²  Norbert Metzdorf⁵  Armin Furtwaengler⁵  Yufeng Liu³  Dacheng Liu¹  Nicolas Roche⁴  Daniel Dusser⁴  Jean-Louis Paillasseur⁶  Pierre-Régis Burgel⁴ 

[1] Boehringer Ingelheim Pharma GmbH & Co KG, Ridgefield, CT, USA;Respiratory Division, Katholieke Universiteit Leuven, University Hospital, Leuven, KU, Belgium;University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;Université Paris Descartes, Sorbonne Paris Cité, Paris, France;Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany;Clindatafirst, Clamart, France

关键词: Tiotropium;    Exacerbations;    COPD;    Mortality;   

Others  :  790256
DOI  :  10.1186/1465-9921-15-64

 received in 2013-12-10, accepted in 2014-06-04,  发布年份 2014

【 摘 要 】

Background

Inhaled therapies reduce risk of chronic obstructive pulmonary disease (COPD) exacerbations, but their effect on mortality is less well established. We hypothesized that heterogeneity in baseline mortality risk influenced the results of drug trials assessing mortality in COPD.

Methods

The 5706 patients with COPD from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study that had complete clinical information for variables associated with mortality (age, forced expiratory volume in 1 s, St George’s Respiratory Questionnaire, pack-years and body mass index) were classified by cluster analysis. Baseline risk of mortality between clusters, and impact of tiotropium were evaluated during the 4-yr follow up.

Results

Four clusters were identified, including low-risk (low mortality rate) patients (n = 2339; 41%; cluster 2), and high-risk patients (n = 1022; 18%; cluster 3), who had a 2.6- and a six-fold increase in all-cause and respiratory mortality compared with cluster 2, respectively. Tiotropium reduced exacerbations in all clusters, and reduced hospitalizations in high-risk patients (p < 0.05). The beneficial effect of tiotropium on all-cause mortality in the overall population (hazard ratio, 0.87; 95% confidence interval, 0.75–1.00, p = 0.054) was explained by a 21% reduction in cluster 3 (p = 0.07), with no effect in other clusters.

Conclusions

Large variations in baseline risks of mortality existed among patients in the UPLIFT® study. Inclusion of numerous low-risk patients may have reduced the ability to show beneficial effect on mortality. Future clinical trials should consider selective inclusion of high-risk patients.

【 授权许可】

   
2014 Burgel et al.; licensee BioMed Central Ltd.

【 图 表 】

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