title: The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting β-agonist therapy in COPD.
abstract: 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.
authors.affiliation: Asthma and Allergy Research Group, University of Dundee, Dundee.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Short
authors.affiliation: Asthma and Allergy Research Group, University of Dundee, Dundee.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Williamson
authors.affiliation: Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Dundee.
authors.forename: Douglas H J
authors.initials: DHJ
authors.lastname: Elder
authors.affiliation: Bute Medical School, University of St. Andrews, St. Andrews.
authors.forename: Samuel I W
authors.initials: SIW
authors.lastname: Lipworth
authors.affiliation: Department of Respiratory Medicine, Perth Royal Infirmary, Perth, Scotland.
authors.forename: Stuart
authors.initials: S
authors.lastname: Schembri
authors.affiliation: Asthma and Allergy Research Group, University of Dundee, Dundee. Electronic address: brianlipworth@gmail.com.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000368:Aged; D002423:Cause of Death / Q000639:trends; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage*; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012008:Recurrence; D012189:Retrospective Studies; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D012606:Scotland / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D018680:Cholinergic Antagonists; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide