Limits...
Inhaled drugs to reduce exacerbations in patients with chronic obstructive pulmonary disease: a network meta-analysis.

Puhan MA, Bachmann LM, Kleijnen J, Ter Riet G, Kessels AG - BMC Med (2009)

Bottom Line: Conventional meta-analyses established that these drugs reduce COPD exacerbations when separately compared with placebo.If FEV1 was </= 40% predicted, long-acting anticholinergics, inhaled corticosteroids, and combination treatment reduced exacerbations significantly compared with long-acting beta-agonists alone, but not if FEV1 was > 40% predicted.We found no evidence that one single inhaled drug regimen is more effective than another in reducing exacerbations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Horten Centre for Patient Oriented Research and Knowledge Transfer, University of Zurich, Switzerland. mpuhan@jhsph.edu

ABSTRACT

Background: Most patients with chronic obstructive pulmonary disease (COPD) receive inhaled long-acting bronchodilators and inhaled corticosteroids. Conventional meta-analyses established that these drugs reduce COPD exacerbations when separately compared with placebo. However, there are relatively few head-to-head comparisons and conventional meta-analyses focus on single comparisons rather than on a simultaneous analysis of competing drug regimens that would allow rank ordering of their effectiveness. Therefore we assessed, using a network meta-analytic technique, the relative effectiveness of the common inhaled drug regimes used to reduce exacerbations in patients with COPD.

Methods: We conducted a systematic review and searched existing systematic reviews and electronic databases for randomized trials of >/= 4 weeks' duration that assessed the effectiveness of inhaled drug regimes on exacerbations in patients with stable COPD. We extracted participants and intervention characteristics from included trials and assessed their methodological quality. For each treatment group we registered the proportion of patients with >/= 1 exacerbation during follow-up. We used treatment-arm based logistic regression analysis to estimate the absolute and relative effects of inhaled drug treatments while preserving randomization within trials.

Results: We identified 35 trials enrolling 26,786 patients with COPD of whom 27% had >/= 1 exacerbation. All regimes reduced exacerbations statistically significantly compared with placebo (odds ratios ranging from 0.71 (95% confidence interval [CI] 0.64 to 0.80) for long-acting anticholinergics to 0.78 (95% CI 0.70 to 0.86) for inhaled corticosteroids). Compared with long-acting bronchodilators alone, combined treatment was not more effective (comparison with long-acting beta-agonists: odds ratio 0.93 [95% CI 0.84 to 1.04] and comparison with long-acting anticholinergics: odds ratio 1.02 [95% CI 0.90 to 1.16], respectively). If FEV1 was 40% predicted. This effect modification was significant for inhaled corticosteroids (P = 0.02 for interaction) and combination treatment (P = 0.01) but not for long-acting anticholinergics (P = 0.46). A limitation of this analysis is its exclusive focus on exacerbations and lack of FEV1 data for individual patients.

Conclusion: We found no evidence that one single inhaled drug regimen is more effective than another in reducing exacerbations. Inhaled corticosteroids when added to long-acting beta-agonists reduce exacerbations only in patients with COPD with FEV1

Show MeSH

Related in: MedlinePlus

Treatment comparisons. Comparisons of long-acting anticholinergics, inhaled corticosteroids and the combination of long-acting beta-agonists + inhaled corticosteroids with long-acting beta-agonists alone stratified for trials including patients with an FEV1 > or ≤ 40% predicted.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2636836&req=5

Figure 3: Treatment comparisons. Comparisons of long-acting anticholinergics, inhaled corticosteroids and the combination of long-acting beta-agonists + inhaled corticosteroids with long-acting beta-agonists alone stratified for trials including patients with an FEV1 > or ≤ 40% predicted.

Mentions: When we analyzed patients with FEV1 ≤ 40% (n = 9,434, mean FEV1 = 37% predicted), long-acting anticholinergics (odds ratio 0.83; 95% CI 0.71 to 0.98), inhaled corticosteroids (odds ratio 0.75; 95% CI 0.57 to 1.00), and combination treatment (odds ratio 0.79; 95% CI 0.67 to 0.93) reduced exacerbations significantly compared with long-acting beta-agonists alone (Figure 3). In patients with FEV1 > 40% predicted (n = 17,352, mean FEV1 = 46% predicted), there were no differences between treatments. Thus, the difference between point estimates in patients with FEV1 ≤ or > 40% was small for long-acting anticholinergics (0.09) but larger for inhaled corticosteroids (0.35) and combination treatment (0.26). This effect modification was confirmed when we tested for effect modification formally (P = 0.46 for long-acting anticholinergics, P = 0.02 for inhaled corticosteroids, and P = 0.01 for combination treatment). Effects of long-acting anticholinergics and combination treatment did not differ significantly (odds ratio 0.94; 95% CI 0.80 to 1.11). There was no effect modification when stratified for FEV1 ≤ or > 50%. In the other stratified analyses (stratified for treatment duration of ≤ and > 6 months and ≤ and > 12 months as well as for definition of exacerbation), we did not observe any influence of treatment duration or the definition of exacerbations on (relative) treatment effects.


Inhaled drugs to reduce exacerbations in patients with chronic obstructive pulmonary disease: a network meta-analysis.

Puhan MA, Bachmann LM, Kleijnen J, Ter Riet G, Kessels AG - BMC Med (2009)

Treatment comparisons. Comparisons of long-acting anticholinergics, inhaled corticosteroids and the combination of long-acting beta-agonists + inhaled corticosteroids with long-acting beta-agonists alone stratified for trials including patients with an FEV1 > or ≤ 40% predicted.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2636836&req=5

Figure 3: Treatment comparisons. Comparisons of long-acting anticholinergics, inhaled corticosteroids and the combination of long-acting beta-agonists + inhaled corticosteroids with long-acting beta-agonists alone stratified for trials including patients with an FEV1 > or ≤ 40% predicted.
Mentions: When we analyzed patients with FEV1 ≤ 40% (n = 9,434, mean FEV1 = 37% predicted), long-acting anticholinergics (odds ratio 0.83; 95% CI 0.71 to 0.98), inhaled corticosteroids (odds ratio 0.75; 95% CI 0.57 to 1.00), and combination treatment (odds ratio 0.79; 95% CI 0.67 to 0.93) reduced exacerbations significantly compared with long-acting beta-agonists alone (Figure 3). In patients with FEV1 > 40% predicted (n = 17,352, mean FEV1 = 46% predicted), there were no differences between treatments. Thus, the difference between point estimates in patients with FEV1 ≤ or > 40% was small for long-acting anticholinergics (0.09) but larger for inhaled corticosteroids (0.35) and combination treatment (0.26). This effect modification was confirmed when we tested for effect modification formally (P = 0.46 for long-acting anticholinergics, P = 0.02 for inhaled corticosteroids, and P = 0.01 for combination treatment). Effects of long-acting anticholinergics and combination treatment did not differ significantly (odds ratio 0.94; 95% CI 0.80 to 1.11). There was no effect modification when stratified for FEV1 ≤ or > 50%. In the other stratified analyses (stratified for treatment duration of ≤ and > 6 months and ≤ and > 12 months as well as for definition of exacerbation), we did not observe any influence of treatment duration or the definition of exacerbations on (relative) treatment effects.

Bottom Line: Conventional meta-analyses established that these drugs reduce COPD exacerbations when separately compared with placebo.If FEV1 was </= 40% predicted, long-acting anticholinergics, inhaled corticosteroids, and combination treatment reduced exacerbations significantly compared with long-acting beta-agonists alone, but not if FEV1 was > 40% predicted.We found no evidence that one single inhaled drug regimen is more effective than another in reducing exacerbations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Horten Centre for Patient Oriented Research and Knowledge Transfer, University of Zurich, Switzerland. mpuhan@jhsph.edu

ABSTRACT

Background: Most patients with chronic obstructive pulmonary disease (COPD) receive inhaled long-acting bronchodilators and inhaled corticosteroids. Conventional meta-analyses established that these drugs reduce COPD exacerbations when separately compared with placebo. However, there are relatively few head-to-head comparisons and conventional meta-analyses focus on single comparisons rather than on a simultaneous analysis of competing drug regimens that would allow rank ordering of their effectiveness. Therefore we assessed, using a network meta-analytic technique, the relative effectiveness of the common inhaled drug regimes used to reduce exacerbations in patients with COPD.

Methods: We conducted a systematic review and searched existing systematic reviews and electronic databases for randomized trials of >/= 4 weeks' duration that assessed the effectiveness of inhaled drug regimes on exacerbations in patients with stable COPD. We extracted participants and intervention characteristics from included trials and assessed their methodological quality. For each treatment group we registered the proportion of patients with >/= 1 exacerbation during follow-up. We used treatment-arm based logistic regression analysis to estimate the absolute and relative effects of inhaled drug treatments while preserving randomization within trials.

Results: We identified 35 trials enrolling 26,786 patients with COPD of whom 27% had >/= 1 exacerbation. All regimes reduced exacerbations statistically significantly compared with placebo (odds ratios ranging from 0.71 (95% confidence interval [CI] 0.64 to 0.80) for long-acting anticholinergics to 0.78 (95% CI 0.70 to 0.86) for inhaled corticosteroids). Compared with long-acting bronchodilators alone, combined treatment was not more effective (comparison with long-acting beta-agonists: odds ratio 0.93 [95% CI 0.84 to 1.04] and comparison with long-acting anticholinergics: odds ratio 1.02 [95% CI 0.90 to 1.16], respectively). If FEV1 was 40% predicted. This effect modification was significant for inhaled corticosteroids (P = 0.02 for interaction) and combination treatment (P = 0.01) but not for long-acting anticholinergics (P = 0.46). A limitation of this analysis is its exclusive focus on exacerbations and lack of FEV1 data for individual patients.

Conclusion: We found no evidence that one single inhaled drug regimen is more effective than another in reducing exacerbations. Inhaled corticosteroids when added to long-acting beta-agonists reduce exacerbations only in patients with COPD with FEV1

Show MeSH
Related in: MedlinePlus