title: Impact of long-acting bronchodilators and exposure to inhaled corticosteroids on mortality in COPD: a real-life retrospective cohort study.
abstract: BACKGROUND
  We performed a real-life retrospective analysis to assess the impact of long-acting bronchodilator therapy and associated exposure to inhaled corticosteroids (ICS) on all-cause and cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  We used record linkage data from patients with a diagnosis of COPD in Tayside, Scotland, between 2001 and 2010. All-cause and cardiovascular mortality were assessed using Cox proportional hazard regression.
  
  
  RESULTS
  A total of 4,133 patients were included, mean FEV1 of 59.5%, mean age of 68.9 years and mean follow-up of 4.6 years. There were 623 who were exposed to long-acting bronchodilators only and 3,510 to long-acting bronchodilators plus ICS. 1,372 patients (33%) died during the study period. Compared with controls taking only long-acting bronchodilators either alone or in combination, all-cause mortality was reduced in patients taking long-acting muscarinic antagonist (LAMA) + ICS as dual therapy: adjusted hazard ratio 0.62 (95% CI 0.45-0.85), but not by long-acting beta-agonist (LABA) + ICS: adjusted hazard ratio 1.02 (95% CI 0.80-1.31). Cardiovascular mortality was not reduced by dual therapy with either LABA or LAMA and concomitant ICS exposure. All-cause and cardiovascular mortality were both reduced in patients taking triple therapy with LABA + LAMA + ICS: adjusted hazard ratio 0.51 (95% CI 0.41-0.64) and 0.56 (95% CI 0.35-0.90), respectively.
  
  
  CONCLUSIONS
  In patients exposed to ICS, concomitant use of LAMA alone as dual therapy or in combination with LABA as triple therapy were associated with reductions in all-cause mortality, while concomitant use of LABA without LAMA conferred no reduction. Moreover, only triple therapy was found to confer benefits on cardiovascular mortality.
authors: Scottish Centre for Respiratory Research, Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK.
authors: Arvind
authors: A
authors: Manoharan
authors: Phillip M
authors: PM
authors: Short
authors: William J
authors: WJ
authors: Anderson
authors: Brian J
authors: BJ
authors: Lipworth
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D002423:Cause of Death; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D012606:Scotland; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists