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Meta-Analysis
. 2006 Apr 19;2006(2):CD001387.
doi: 10.1002/14651858.CD001387.pub2.

Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease

S Appleton  1 , T Jones, P Poole, L Pilotto, R Adams, T J Lasserson, B Smith, J Muhammad
Affiliations
Meta-Analysis

Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease

S Appleton et al. Cochrane Database Syst Rev. .

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with short-acting beta-2 agonists (SABA) and anticholinergic bronchodilator medications, and both are recommended in COPD guidelines. These medications have different mechanisms of action and therefore could have an additive effect when combined.

Objectives: To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and short- acting beta-2 agonist therapy in patients with stable COPD.

Search strategy: The Cochrane Airways Group Specialised Register of Trials was searched. Bibliographies were checked to identify relevant cross-references. Drug companies were contacted for relevant trial data. The searches are current to August 2005.

Selection criteria: All randomised controlled trials comparing at least 4 weeks of treatment with an anticholinergic agent (ipratropium bromide) alone or in combination with a beta-2 agonist (short acting) versus the beta-2 agonist alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD.

Data collection and analysis: Data extraction and study quality assessment was performed independently by three reviewers. Authors of studies and relevant manufacturers were contacted if data were missing.

Main results: Eleven studies (3912 participants) met the inclusion criteria of the review. Small benefits of ipratropium over a short-acting beta-2 agonist were demonstrated on lung function outcomes. There were small benefits in favour of ipratropium on quality of life (HRQL), as well as a reduction in the requirement for oral steroids. Combination therapy with ipratropium plus a short-acting beta-2 agonist conferred benefits over a short-acting beta-2 agonist alone in terms of post-bronchodilator lung function. There was no significant benefit of combination therapy in subjective improvements in HRQL, but again there was a reduction in the requirement for oral steroids.

Authors' conclusions: The available data from the trials included in this review suggest that the advantage of regular long term use of ipratropium alone or in combination with a short-acting beta-2 agonist or over a beta-2 agonist alone are small, if the aim is to improve lung function, symptoms and exercise tolerance. Until further data are available, the strategy of providing a short-acting beta-2 agonist on a PRN basis, and then either continuing with the short-acting beta-2 agonist regularly or conducting an "n of 1" trial of regular beta-2 agonist or regular anticholinergic to determine the treatment that gives the best relief of symptoms (and continuing with it), would seem cost effective. This strategy does need formal evaluation. Patient preference is also important, as is the relative importance of avoiding the use of systemic corticosteroids.

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Conflict of interest statement

None known.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
2
2
Graphic to demonstrate that in the treatment of COPD with either ipratropium or short‐acting beta‐agonist, 15 people would need to be treated ipratropium in order to prevent one person requiring a course oral steroids.
3
3
Graphic to demonstrate that in the treatment of COPD with either combination ipratropium and short‐acting beta‐agonist or short‐acting beta‐agonist alone, 20 people would need to be treated ipratropium in order to prevent one person requiring a course oral steroids.
4
4
Funnel plot demonstrating possible publication bias
1.1
1.1. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 1 Test day 85 mean baseline FEV1 (absolute, litres).
1.2
1.2. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 2 Test day 85 mean peak FEV1 response (change from day 85 baseline, litres).
1.3
1.3. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 3 Test day 85 mean FEV1 AUC (absolute, litres).
1.4
1.4. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 4 Test day 85 mean baseline FVC (absolute, litres).
1.5
1.5. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 5 Test day peak FVC.
1.6
1.6. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 6 Test day FVC AUC.
1.7
1.7. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 7 Symptom scores.
1.8
1.8. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 8 Number of subjects with medication related adverse events.
1.9
1.9. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 9 HRQL‐ Chronic Respiratory Disease Questionnaire: absolute scores.
1.10
1.10. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 10 Number of subjects adding or increasing systemic (oral) corticosteroids.
1.11
1.11. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 11 Borg Dyspnoea Index.
1.12
1.12. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 12 Borg dyspnoea score‐ reduction of 1 unit.
1.13
1.13. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 13 Six minute walk distance.
1.14
1.14. Analysis
Comparison 1 Ipratropium bromide versus short acting beta‐2 agonist via nebuliser or MDI, Outcome 14 Six minute walk distance test‐improved at least 30 metres.
2.1
2.1. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 1 Test day 85 baseline FEV1(absolute, litres).
2.2
2.2. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 2 Test day (last:29 or 85) peak FEV1 response (litres).
2.3
2.3. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 3 Test day 85 FEV1 AUC (0‐8 hours), litres/hour.
2.4
2.4. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 4 Test day 85 baseline FVC.
2.5
2.5. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 5 Test day (last: 29 or 85) peak FVC response (litres).
2.6
2.6. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 6 Test day 85 FVC AUC (0‐8 hours), litres/hour.
2.7
2.7. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 7 Symptom Scores.
2.8
2.8. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 8 Six minute walk distance (m).
2.9
2.9. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 9 Test day HRQL‐Chronic Respiratory Disease Questionnaire.
2.10
2.10. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 10 Number of subjects with at least one exacerbation during 12 week study.
2.11
2.11. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 11 Number of subjects adding or increasing systemic (oral) corticosteroids.
2.12
2.12. Analysis
Comparison 2 Ipratropium bromide + short acting beta‐2 agonist v. short‐acting beta‐2 agonist via nebuliser or MDI, Outcome 12 Number of subjects experiencing adverse event related to medication.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD001387

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MeSH terms