title: Tiotropium reduces risk of exacerbations irrespective of previous use of inhaled anticholinergics in placebo-controlled clinical trials.
abstract: BACKGROUND
  Data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids. Analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials.
  
  
  METHODS
  A pooled analysis of randomized, double-blind, placebo-controlled, parallel-group tiotropium trials of at least six months' duration was performed. Trials had similar inclusion and exclusion criteria. Exacerbation definition was standardized. Patients were divided into two groups, ie, D (anticholinergics discontinued at randomization, previously prescribed) and ND (anticholinergics not discontinued, not previously prescribed).
  
  
  RESULTS
  Demographics were balanced between the D (n = 5846) and ND (n = 6317) groups, except for higher cumulative smoking (56 pack-years versus 48 pack-years), lower forced expiratory volume in one second (FEV(1))/forced vital capacity (43% versus 48%), and lower baseline FEV(1) (35.8% predicted versus 42.4% predicted) in the D group. In both groups, tiotropium reduced the risk for an exacerbation (hazard ratio [HR] = 0.83, P < 0.0001 [D] versus 0.79, P < 0.0001 [ND]) and a hospitalized exacerbation (HR = 0.85, P = 0.0467 versus 0.79, P = 0.0094). Tiotropium reduced the number of exacerbations per patient-year (rate ratio [RR] = 0.82, P < 0.0001 [D] versus RR = 0.80, P < 0.0001 [ND]) and associated hospitalizations per patient-year (RR = 0.88, P = 0.015 [D] versus RR = 0.74, P < 0.0001 [ND]).
  
  
  CONCLUSIONS
  Tiotropium reduced exacerbations in patients who did and did not have anticholinergics discontinued upon randomization in clinical trials.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, CA, USA. ccooper@mednet.ucla.edu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Cooper
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Inge
authors.initials: I
authors.lastname: Leimer
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D019317:Evidence-Based Medicine; D005260:Female; D005541:Forced Expiratory Volume; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide