title: Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics: a post hoc analysis of the TIOSPIR trial.
abstract: BACKGROUND
  Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects.
  
  
  OBJECTIVE
  The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 μg.
  
  
  METHODS
  A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease.
  
  
  RESULTS
  Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups.
  
  
  CONCLUSIONS
  Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wise
authors.affiliation: Respiratory Medicine, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: Allergy Centre, Odense University Hospital, Odense C, Denmark.
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.affiliation: Service de Pneumologie, Hôpital Cochin, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
authors.affiliation: Medical Affairs, Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Metzdorf
authors.affiliation: Global Clinical Operations, Biometry and Data Management, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Müller
authors.affiliation: Medical Affairs, Boehringer Ingelheim Pharma Ltd, Bracknell, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Fowler
authors.affiliation: Department of Medicine, Pulmonary Critical Care Center, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D018680:Cholinergic Antagonists / Q000008:administration & dosage*; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D000069447:Tiotropium Bromide / Q000008:administration & dosage*; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D018680:Cholinergic Antagonists; D000069447:Tiotropium Bromide