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Pharmacologic Treatments for Chronic Obstructive Pulmonary Disease: A Mixed‐Treatment Comparison Meta‐analysis
Author(s) -
Baker William L.,
Baker Erica L.,
Coleman Craig I.
Publication year - 2009
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.29.8.891
Subject(s) - medicine , copd , exacerbation , placebo , odds ratio , randomized controlled trial , corticosteroid , tiotropium bromide , combination therapy , bronchodilator , anesthesia , asthma , lung , lung function , pathology , alternative medicine
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 β 2 ‐agonists, tiotropium, inhaled corticosteroids, and/or combination therapy with an inhaled corticosteroid and a long‐acting β 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 β 2 ‐agonists, tiotropium, inhaled corticosteroids, and combination inhaled corticosteroid‐long‐acting β 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 β 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 β 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 β 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 β 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 β 2 ‐agonists. Conclusion : Our MTC meta‐analysis provides a useful and comprehensive evaluation of the beneficial effects of various therapeutic drug classes on outcomes in patients with COPD. Combination inhaled corticosteroid‐long‐acting β 2 ‐agonist therapy had the greatest positive effect on outcomes. Of the bronchodilator monotherapies, tiotropium was associated with lower odds of having an exacerbation or withdrawing from a study compared with long‐acting β 2 ‐agonists.