, Volume 192, Issue 5, pp 649–652

Impact of Long-Acting Bronchodilators and Exposure to Inhaled Corticosteroids on Mortality in COPD: A Real-Life Retrospective Cohort Study

  • Arvind Manoharan
  • Phillip M. Short
  • William J. Anderson
  • Brian J. Lipworth



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).


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.


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.


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.


COPD Long-acting beta-agonists Long-acting muscarinic antagonists Inhaled corticosteroids 


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Arvind Manoharan
    • 1
  • Phillip M. Short
    • 1
  • William J. Anderson
    • 1
  • Brian J. Lipworth
    • 1
  1. 1.Scottish Centre for Respiratory Research, Division of Cardiovascular and Diabetes Medicine, Medical Research InstituteUniversity of Dundee, Ninewells Hospital and Medical SchoolDundeeScotland, UK

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