title: Tiotropium Respimat inhaler and the risk of death in COPD.
abstract: BACKGROUND
  Tiotropium delivered at a dose of 5 μg with the Respimat inhaler showed efficacy similar to that of 18 μg of tiotropium delivered with the HandiHaler inhalation device in placebo-controlled trials involving patients with chronic obstructive pulmonary disease (COPD). Although tiotropium HandiHaler was associated with reduced mortality, as compared with placebo, more deaths were reported with tiotropium Respimat than with placebo.
  
  
  METHODS
  In this randomized, double-blind, parallel-group trial involving 17,135 patients with COPD, we evaluated the safety and efficacy of tiotropium Respimat at a once-daily dose of 2.5 μg or 5 μg, as compared with tiotropium HandiHaler at a once-daily dose of 18 μg. Primary end points were the risk of death (noninferiority study, Respimat at a dose of 5 μg or 2.5 μg vs. HandiHaler) and the risk of the first COPD exacerbation (superiority study, Respimat at a dose of 5 μg vs. HandiHaler). We also assessed cardiovascular safety, including safety in patients with stable cardiac disease.
  
  
  RESULTS
  During a mean follow-up of 2.3 years, Respimat was noninferior to HandiHaler with respect to the risk of death (Respimat at a dose of 5 μg vs. HandiHaler: hazard ratio, 0.96; 95% confidence interval [CI], 0.84 to 1.09; Respimat at a dose of 2.5 μg vs. HandiHaler: hazard ratio, 1.00; 95% CI, 0.87 to 1.14) and not superior to HandiHaler with respect to the risk of the first exacerbation (Respimat at a dose of 5 μg vs. HandiHaler: hazard ratio, 0.98; 95% CI, 0.93 to 1.03). Causes of death and incidences of major cardiovascular adverse events were similar in the three groups.
  
  
  CONCLUSIONS
  Tiotropium Respimat at a dose of 5 μg or 2.5 μg had a safety profile and exacerbation efficacy similar to those of tiotropium HandiHaler at a dose of 18 μg in patients with COPD. (Funded by Boehringer Ingelheim; TIOSPIR ClinicalTrials.gov number, NCT01126437.).
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. rwise@jhmi.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wise
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.forename: Daniel
authors.initials: D
authors.lastname: Cotton
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.forename: Theresa
authors.initials: T
authors.lastname: Devins
authors.forename: Bernd
authors.initials: B
authors.lastname: Disse
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joseph
authors.forename: Sabine
authors.initials: S
authors.lastname: Kattenbeck
authors.forename: Michael
authors.initials: M
authors.lastname: Koenen-Bergmann
authors.forename: Gordon
authors.initials: G
authors.lastname: Pledger
authors.forename: Peter
authors.initials: P
authors.lastname: Calverley
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D012306:Risk; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects; D013147:Spirometry; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide