Pharmacologic treatments for chronic obstructive pulmonary disease: a mixed-treatment comparison meta-analysis.
OBJECTIVE
To assess the comparative efficacy of pharmacologic agents for the maintenance treatment of chronic obstructive pulmonary disease (COPD).


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


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


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.
Baker
William L
WL
Hartford Hospital Drug Information Center, Hartford, Connecticut 06102-5037, USA.
Baker
Erica L
EL
Coleman
Craig I
CI
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D006801:Humans; D010349:Patient Compliance; D010352:Patient Dropouts; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012602:Scopolamine Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D000069447:Tiotropium Bromide
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D010919:Placebos; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide