Pharmacologic treatments for chronic obstructive pulmonary disease: a mixed-treatment comparison meta-analysis

Pharmacotherapy. 2009 Aug;29(8):891-905. doi: 10.1592/phco.29.8.891.


Study objective: To assess the comparative efficacy of pharmacologic agents for the maintenance treatment of chronic obstructive pulmonary disease (COPD).

Design: Traditional and mixed-treatment comparison (MTC) meta-analyses of randomized controlled trials.

Patients: A total of 31,020 patients with COPD from 43 trials.

Measurements and main results: A systematic literature search of various databases (through October 2007) was performed to identify randomized controlled trials of long-acting beta(2)-agonists, tiotropium, inhaled corticosteroids, and/or combination therapy with an inhaled corticosteroid and a long-acting beta(2)-agonist in patients with COPD. Forty-three trials were included. Both meta-analyses were used to evaluate the occurrence of one or more episodes of COPD exacerbation, overall mortality, and patient withdrawal rates. With MTC analysis, long-acting beta(2)-agonists, tiotropium, inhaled corticosteroids, and combination inhaled corticosteroid-long-acting beta(2)-agonist therapy each decreased the odds of having an exacerbation by 16%, 31%, 15%, and 24%, respectively, compared with placebo. Moreover, tiotropium use reduced the odds of having at least one exacerbation by 18% compared with long-acting beta(2)-agonists and by 19% compared with inhaled corticosteroids alone. Each of the four drug classes was associated with significant odds reductions in patient withdrawals (26-41%) compared with placebo, and both tiotropium and combination therapy significantly decreased the odds of patient withdrawals compared with long-acting beta(2)-agonists or inhaled corticosteroids alone. Only combination therapy was associated with a mortality benefit, showing a 29% reduction compared with placebo and a 25% reduction compared with long-acting beta(2)-agonists alone. Compared with combination therapy, tiotropium use reduced exacerbations by 9% and increased mortality by only 4%. These findings did not demonstrate significant changes in the sensitivity or subgroup analyses, which were performed to evaluate the effect of heterogeneity among the included studies.

Conclusions: Combination inhaled corticosteroid-long-acting beta(2)-agonist therapy was associated with the greatest positive effect on outcomes in patients with COPD. Of the bronchodilator monotherapies, tiotropium was associated with lower odds of having a COPD exacerbation or withdrawal from a study compared with long-acting beta(2)-agonists.

Publication types

  • Meta-Analysis

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Adrenergic beta-Agonists / administration & dosage*
  • Adrenergic beta-Agonists / adverse effects
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Delayed-Action Preparations
  • Drug Therapy, Combination
  • Humans
  • Patient Compliance
  • Patient Dropouts
  • Placebos
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Randomized Controlled Trials as Topic
  • Scopolamine Derivatives / adverse effects
  • Scopolamine Derivatives / therapeutic use*
  • Tiotropium Bromide


  • Adrenal Cortex Hormones
  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Delayed-Action Preparations
  • Placebos
  • Scopolamine Derivatives
  • Tiotropium Bromide