title: One-year mortality associated with COPD treatment: a comparison of tiotropium and long-acting beta2-agonists in three Italian regions: results from the OUTPUL study.
abstract: Long-acting bronchodilators, i.e. beta-2-agonists (LABA) and tiotropium are commonly used in COPD treatment. Choice of a specific agent is based on effectiveness and safety. Evidence yields controversial results with respect to mortality. The present study compared one-year mortality associated to treatment with tiotropium versus LABA.
  
  
  
  A population-based cohort study using data from Italian health information systems was performed. Patients aged 45+ years, discharged with COPD diagnosis in 2006-2009 were identified. Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled. The main analysis was restricted to naïve users (no prior use of either LABA or tiotropium). We used 'intention to treat' (ITT) and 'as treated' (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score. In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group.
  
  
  
  Among the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both. Overall mean age was 74 years and the mortality rate was 122/1000 person-years (py) at the ITT analysis and 108/1000 py at the AT analysis. The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94-1.20) at the ITT analysis and 1.00 (95%CI: 0.93-1.08) at the AT analysis. Results were robust in sensitivity analysis.
  
  
  
  In this real-world study use of tiotropium was not associated with an increased risk of one-year mortality compared with LABA. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kirchmayer
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cascini
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Nera
authors.initials: N
authors.lastname: Agabiti
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Di Martino
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bauleo
authors.affiliation: Emilia-Romagna Regional Health and Social Care Agency, Bologna, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Formoso
authors.affiliation: Emilia-Romagna Regional Health and Social Care Agency, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Voci
authors.affiliation: Department of Respiratory Physiology, Catholic University, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pistelli
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Patorno
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Davoli
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D000069447:Tiotropium Bromide / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D000069447:Tiotropium Bromide
keywords: COPD; cohort; drug treatment; mortality; pharmacoepidemiology
references.citation: Lancet. 2007 Sep 1;370(9589):765-73
references.pmid: 17765526
references.citation: Eur J Epidemiol. 2007;22(4):267-72
references.pmid: 17342451
references.citation: Cochrane Database Syst Rev. 2013 May 31;(5):CD007891
references.pmid: 23728670
references.citation: Thorax. 2013 Nov;68(11):1066-7
references.pmid: 23744029
references.citation: Chest. 2004 Jun;125(6):2309-21
references.pmid: 15189956
references.citation: Pharmacoepidemiol Drug Saf. 2016 May;25(5):578-89
references.pmid: 26822968
references.citation: Chest. 2010 Jan;137(1):1-3
references.pmid: 20051395
references.citation: Respirology. 2013 Jan;18(1):147-53
references.pmid: 22985270
references.citation: Pulm Pharmacol Ther. 2012 Feb;25(1):40-7
references.pmid: 22085775
references.citation: Ann Intern Med. 2011 May 3;154(9):583-92
references.pmid: 21536937
references.citation: Drugs. 2012 Jan 22;72(2):273-300
references.pmid: 22217233
references.citation: N Engl J Med. 2011 Mar 24;364(12):1093-1103
references.pmid: 21428765
references.citation: Can Respir J. 2003 May-Jun;10 Suppl A:11A-65A
references.pmid: 12861361
references.citation: Chest. 2010 Jan;137(1):20-30
references.pmid: 19592475
references.citation: Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65
references.pmid: 22878278
references.citation: COPD. 2014 Aug;11(4):414-23
references.pmid: 24090036
references.citation: Curr Opin Pulm Med. 2010 Mar;16(2):97-105
references.pmid: 20019615
references.citation: Int J Chron Obstruct Pulmon Dis. 2013;8:117-25
references.pmid: 23515335
references.citation: J Gen Intern Med. 2006 Oct;21(10):1011-9
references.pmid: 16970553
references.citation: Thorax. 2013 Jan;68(1):114-6
references.pmid: 22764216
references.citation: Epidemiol Prev. 2012 May-Aug;36(3-4):172-9
references.pmid: 22828230
references.citation: COPD. 2016 Jun;13(3):293-302
references.pmid: 26514912
references.citation: Pharmacoepidemiol Drug Saf. 2004 Dec;13(12):841-53
references.pmid: 15386709
references.citation: Cochrane Database Syst Rev. 2014 Mar 26;(3):CD010844
references.pmid: 24671923
references.citation: Cochrane Database Syst Rev. 2012 Sep 12;(9):CD009157
references.pmid: 22972134
references.citation: Drug Saf. 2007;30(12):1151-60
references.pmid: 18035867
references.citation: N Engl J Med. 2010 Sep 16;363(12):1097-9
references.pmid: 20843240
references.citation: Int J Chron Obstruct Pulmon Dis. 2009;4:253-63
references.pmid: 19657399
references.citation: BMJ Open. 2012 May 22;2(3):
references.pmid: 22619266
references.citation: JAMA. 2008 Sep 24;300(12):1439-50
references.pmid: 18812535
references.citation: Ann Intern Med. 2011 Aug 2;155(3):179-91
references.pmid: 21810710
references.citation: Expert Opin Drug Saf. 2015;14(11):1759-72
references.pmid: 26401729
references.citation: COPD. 2008 Aug;5(4):229-34
references.pmid: 18671148