title: Tiotropium might improve survival in subjects with COPD at high risk of mortality.
abstract: 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.
authors.affiliation: Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France. pierre-regis.burgel@cch.aphp.fr.
authors.forename: Pierre-Régis
authors.initials: PR
authors.lastname: Burgel
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paillasseur
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
authors.forename: Nicolas
authors.initials: N
authors.lastname: Roche
authors.forename: Dacheng
authors.initials: D
authors.lastname: Liu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Armin
authors.initials: A
authors.lastname: Furtwaengler
authors.forename: Norbert
authors.initials: N
authors.lastname: Metzdorf
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D015996:Survival Rate / Q000639:trends; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide