The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease.
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.
Kliber
Agnes
A
Department of Medicine (Respiratory Division), University of British Columbia, 6040 Iona Drive, Vancouver, V6T 2E8, Canada.
Lynd
Larry D
LD
Sin
Don D
DD
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D004338:Drug Combinations; D019317:Evidence-Based Medicine; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004338:Drug Combinations
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