title: The impact of adherence to inhaled drugs on 5-year survival in COPD patients: a time dependent approach.
abstract: Whether inhaled medications improve long-term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question. The purpose of this study is to assess the impact of adherence to inhaled drug use on 5-year survival in COPD.
  
  
  
  A population-based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs). Individuals (45+ years) discharged after COPD exacerbation in 2006-2009 were enrolled. Inhaled drug daily use during 5-year follow-up was determined through Proportion of Days Covered on the basis of Defined Daily Doses. Five levels of time-dependent exposure were identified: (i) long-acting β2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB. Cox regression models adjusted for baseline (socio-demographic, comorbidities, drug use) and time-dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed.
  
  
  
  A total of 12 124 individuals were studied, 46% women, mean age 73,8 years. Average follow-up time 2,4 year. A total of 3415 subjects died (mortality rate = 11.9 per 100 person years). In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43-1.87). Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79-0.99).
  
  
  
  These findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate-severe COPD patients. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Belleudi
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Di Martino
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cascini
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kirchmayer
authors.affiliation: Department of Respiratory Physiology, Catholic University, Roma, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pistelli
authors.affiliation: Emilia-Romagna Regional Health and Social Care Agency, Bologna, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Formoso
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fusco
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Roma, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Davoli
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Roma, Italy. n.agabiti@deplazio.it.
authors.forename: Nera
authors.initials: N
authors.lastname: Agabiti
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007558:Italy; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents
keywords: adherence; bronchodilators; drug comparative effectiveness; inhaled corticosteroids; pharmacoepidemiology; survival