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

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

Agnes Kliber  1 , Larry D Lynd, Don D Sin
Affiliations
Meta-Analysis

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

Agnes Kliber et al. Respir Res. .

Abstract

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.

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Figures

Figure 1
Figure 1
Flow Diagram Outlining the Search Strategy.
Figure 2
Figure 2
The Effects of Inhaled Corticosteroid/Long-Acting Beta-2 Agonist Combination on Total Mortality. Abbreviations: BUD/F, budesonide/formoterol combination; CI, confidence interval; ICS/LABA, inhaled corticosteroids/long-acting beta-2 agonist combination; M-H, Mantel-Hanzel; SALM, salmeterol; SFC, salmeterol/fluticasone combination
Figure 3
Figure 3
The Effects of Inhaled Corticosteroid/Long-Acting Beta-2 Agonist Combination on Total Mortality Excluding Calverley et al's Trial [13]. Abbreviations: BUD/F, budesonide/formoterol combination; CI, confidence interval; ICS/LABA, inhaled corticosteroids/long-acting beta-2 agonist combination; M-H, Mantel-Hanzel; SALM, salmeterol; SFC, salmeterol/fluticasone combination
Figure 4
Figure 4
The Effects of Inhaled Corticosteroid/Long-Acting Beta-2 Agonist Combination on Total Mortality Using Clinical Trials That Used Placebo-Treated Patients As The Main Comparator. Abbreviations: BUD/F, budesonide/formoterol combination; CI, confidence interval; ICS/LABA, inhaled corticosteroids/long-acting beta-2 agonist combination; M-H, Mantel-Hanzel; SALM, salmeterol; SFC, salmeterol/fluticasone combination
Figure 5
Figure 5
The Effects of Long-Acting Beta-2 Agonists on Total Mortality. Abbreviations: CI, confidence interval; FORM, formoterol; LABA; long-acting beta-2 agonists; M-H, Mantel-Hanzel; SALM, salmeterol
Figure 6
Figure 6
The Effects of Tiotropium on Total Mortality. Abbreviations: CI, confidence interval; ICS/LABA, inhaled corticosteroids/long-acting beta-2 agonist combination; M-H, Mantel-Hanzel
Figure 7
Figure 7
The Effects of Tiotropium on Total Mortality Using Clinical Trials That Used Placebo or Ipratropium Bromide As The Main Comparator. Abbreviations: CI, confidence interval; ICS/LABA, inhaled corticosteroids/long-acting beta-2 agonist combination; M-H, Mantel-Hanzel
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