The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting β-agonist therapy in COPD

Chest. 2012 Jan;141(1):81-86. doi: 10.1378/chest.11-0038. Epub 2011 Jul 28.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / administration & dosage*
  • Aged
  • Cause of Death / trends
  • Cholinergic Antagonists / administration & dosage
  • Delayed-Action Preparations / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / drug effects
  • Glucocorticoids / administration & dosage*
  • Hospital Mortality / trends
  • Humans
  • Male
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Recurrence
  • Retrospective Studies
  • Scopolamine Derivatives / administration & dosage*
  • Scotland / epidemiology
  • Survival Rate / trends
  • Time Factors
  • Tiotropium Bromide
  • Treatment Outcome
  • Vital Capacity / drug effects


  • Adrenergic beta-Agonists
  • Cholinergic Antagonists
  • Delayed-Action Preparations
  • Glucocorticoids
  • Scopolamine Derivatives
  • Tiotropium Bromide