The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease

Respir Res. 2010 May 11;11(1):56. doi: 10.1186/1465-9921-11-56.


Background: Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD.

Methods: Using MEDLINE, EMBASE and Cochrane Systematic Review databases, we identified high quality randomized controlled trials of tiotropium, formoterol, salmeterol, formoterol/budesonide or salmeterol/fluticasone in COPD that had a follow-up of 6 months or longer and reported on total mortality. Two reviewers independently abstracted data from the original trials and disagreements were resolved by iteration and consensus.

Results: Twenty-seven trials that included 30,495 patients were included in the review. Relative risk (RR) for total mortality was calculated for each of the study and pooled together using a random-effects model. The combination of inhaled corticosteroid (ICS) and long-acting beta-2 agonist (LABA) therapy was associated with reduced total mortality compared with placebo (RR, 0.80; p = 0.005). Neither tiotropium (RR, 1.08; p = 0.61) nor LABA by itself (RR, 0.90; p = 0.21) was associated with mortality.

Conclusions: A combination of ICS and LABA reduced mortality by approximately 20%. Neither tiotropium nor LABA by itself modifies all-cause mortality in COPD.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / therapeutic use*
  • Adrenergic beta-2 Receptor Agonists*
  • Adrenergic beta-Agonists / therapeutic use*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Chi-Square Distribution
  • Cholinergic Antagonists / therapeutic use*
  • Drug Combinations
  • Evidence-Based Medicine
  • Humans
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Drug Combinations