Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease
- PMID: 16856113
- PMCID: PMC7200053
- DOI: 10.1002/14651858.CD006101
Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease
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 long acting beta-2 agonists (LABAs) and anticholinergic bronchodilator medications, both of which are recommended in COPD guidelines. These medications have different mechanisms of action and therefore theoretically could have an additive effect when combined. As these medications are prescribed in COPD as long term therapy, it is important to assemble reliable evidence on their relative and additive effects.
Objectives: To compare the relative efficacy and safety of regular long term use (at least four weeks) of ipratropium bromide and LABA in patients with stable COPD. Comparisons were made between single agents and in combination versus LABAs alone.
Search strategy: We searched the Cochrane Airways Group Specialised Register of Trials (August 2005) and reference lists of articles. We also contacted drug companies for relevant trial data.
Selection criteria: All randomised controlled trials comparing treatment for at least four weeks with an anticholinergic agent (ipratropium bromide) alone or in combination with LABA versus LABA alone, delivered via metered dose inhaler or nebuliser, in non-asthmatic adult subjects with stable COPD.
Data collection and analysis: Three review authors independently performed data extraction and study quality assessment. We contacted study authors and pharmaceutical companies for missing data.
Main results: Seven studies met the inclusion criteria of the review (2652 participants). Monotherapy comparison (six studies): There was a significantly greater change in favour of salmeterol in morning PEF and FEV1. There were no significant differences in quality of life, exacerbations, or symptoms. Formoterol appeared to confer some benefits over ipratropium treatment in terms of morning peak flow. Combination comparison (three studies): There was a significant improvement in post-bronchodilator lung function, supplemental short-acting beta-agonist use and HRQL in favour of combination therapy compared with salmeterol alone.
Authors' conclusions: The available data from the trials suggest that there is little difference between regular long term use of IpB alone and salmeterol if the aim is to improve COPD symptoms and exercise tolerance. However, salmeterol was more effective in improving lung function variables. In terms of post-bronchodilator lung function, combination therapy conferred modest benefits and a significant improvement in HRQL, and reduced supplemental short-acting beta-agonist requirement, although this effect was not consistent. Additional studies are needed to assess the relative effects of combining therapies, using validated subjective measurements, and should consider concordance and the convenience of people having to use different inhaler devices.
Conflict of interest statement
None known.
Similar articles
-
Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD009157. doi: 10.1002/14651858.CD009157.pub2. Cochrane Database Syst Rev. 2012. PMID: 22972134 Free PMC article.
-
Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2006 Apr 19;2006(2):CD001387. doi: 10.1002/14651858.CD001387.pub2. Cochrane Database Syst Rev. 2006. PMID: 16625543 Free PMC article.
-
Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2015 Oct 22;2015(10):CD008989. doi: 10.1002/14651858.CD008989.pub3. Cochrane Database Syst Rev. 2015. PMID: 26490945 Free PMC article.
-
Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD006829. doi: 10.1002/14651858.CD006829.pub2. Cochrane Database Syst Rev. 2012. PMID: 22972099 Free PMC article.
-
Inhaled corticosteroids versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2011 Oct 5;(10):CD007033. doi: 10.1002/14651858.CD007033.pub2. Cochrane Database Syst Rev. 2011. Update in: Cochrane Database Syst Rev. 2011 Dec 07;(12):CD007033. doi: 10.1002/14651858.CD007033.pub3. PMID: 21975759 Updated.
Cited by
-
Combination inhaled steroid and long-acting beta₂-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2016 Jun 6;2016(6):CD008532. doi: 10.1002/14651858.CD008532.pub3. Cochrane Database Syst Rev. 2016. PMID: 27271056 Free PMC article.
-
An integrative review of systematic reviews related to the management of breathlessness in respiratory illnesses.BMC Pulm Med. 2010 Dec 9;10:63. doi: 10.1186/1471-2466-10-63. BMC Pulm Med. 2010. PMID: 21143887 Free PMC article. Review.
-
Compatible Stability and Aerosol Characteristics of Atrovent® (Ipratropium Bromide) Mixed with Salbutamol Sulfate, Terbutaline Sulfate, Budesonide, and Acetylcysteine.Pharmaceutics. 2020 Aug 15;12(8):776. doi: 10.3390/pharmaceutics12080776. Pharmaceutics. 2020. PMID: 32824123 Free PMC article.
-
Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline.Chest. 2015 Apr;147(4):894-942. doi: 10.1378/chest.14-1676. Chest. 2015. PMID: 25321320 Free PMC article.
-
Guideline Alignment and Medication Concordance in COPD.CHEST Pulm. 2024 Mar;2(1):100017. doi: 10.1016/j.chpulm.2023.100017. Epub 2023 Sep 4. CHEST Pulm. 2024. PMID: 38645884 Free PMC article.
References
References to studies included in this review
Dahl 2001 {Published data only}
-
- Dahl R, Greefhorst LA, Nowak D, Nonikov V, Byrne AM, Thomson MH, et al. Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease. American Journal of Respiratory & Critical Care Medicine 2001; 164:778-84. - PubMed
Mahler 1999 {Published data only}
-
- Goodwin B, Cox F, Anderson W, Wisniewski M, Rickard K. Comparison of salmeterol 42uG BID (SLG) versus ipratropium bromide 36 uG q.i.d. vs placebo on disease specific quality of life in COPD patients: reversible or non-reversible to ventolin. In: American Thoracic Society International Conference. 1999.
-
- Mahler DA, Donohue JF, Barbee RA, Goldman MD, Gross NJ, Wisniewski ME, et al. Efficacy of salmeterol xinafoate in the treatment of COPD. Chest 1999; 115(4):957-65. - PubMed
-
- SLGA4005. A randomized, double-blind, double-dummy, comparative clinical trial of 12-week courses of salmeterol xinafoate versus ipratropium bromide versus placebo (prn ventolin®) in subjects with chronic obstructive pulmonary disease. http://ctr.gsk.co.uk 2005.
Rennard 2001 {Published data only}
-
- Goodwin B, Cox F, Anderson W, Wisniewski M, Rickard K. Comparison of salmeterol 42uG BID (SLG) versus ipratropium bromide 36 uG q.i.d. vs placebo on disease specific quality of life in COPD patients: reversible or non-reversible to ventolin. In: American Thoracic Society International Conference. 1999.
-
- Rennard S, Anderson W, ZuWallack R, Broughton J, Bailey W, Friedman M, et al. Use of a long-acting inhaled Beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease. American Journal of Respiratory & Critical Care Medicine 2001; 163(5):1087-92. - PubMed
-
- SLGA4004. A randomized, double-blind, double-dummy, comparative clinical trial of 12-week courses of salmeterol xinafoate versus ipratropium bromide versus placebo (prn ventolin) in subjects with chronic obstructive pulmonary disease. http://ctr.gsk.co.uk 2005.
SMS40314 {Published data only}
-
- SMS40314. A multicenter, randomized, double-blind, double-dummy, parallel-group, 8-week comparison of salmeterol xinafoate versus ipratropium bromide versus salmeterol xinafoate plus ipratropium bromide versus placebo in subjects with chronic obstructive pulmonary disease. http://ctr.gsk.co.uk 2005.
SMS40315 {Unpublished data only}
-
- SMS40315. A multicenter, randomized, double-blind, double-dummy, parallel group, 8-week comparison of salmeterol xinafoate versus ipratropium bromide versus salmeterol xinafoate plus ipratropium bromide versus placebo in subjects with chronic obstructive pulmonary disease. http://ctr.gsk.co.uk 2005.
Stahl 2002 {Published data only}
-
- Stahl E, Wadbo M, Bengtsson T, Strom K, Lofdahl C-G. Health-related quality of life, symptoms, exercise capacity and lung function during treatment for moderate to severe COPD. Journal of Drug Assessment 2002; 5:81-94.
-
- Wadbo M, Lofdahl CG, Larsson K, Skoogh BE, Tornling G, Arwestrom E, et al. Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study. European Respiratory Journal 2002; 20(5):1138-46. - PubMed
van Noord 2000 {Published data only}
-
- SLGF55. Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium. http:ctr.gsk.co.uk 2005. - PubMed
-
- Noord JA, Munck DR, Bantje TA, Hop WCJ, Bommer AM. Long-term treatment of chronic obstructive pulmonary disease with salmeterol and the additive effect of ipratropium. European Respiratory Journal 2000; 15:878-85. - PubMed
References to studies excluded from this review
Bauer 1975 {Published data only}
-
- Bauer VP, Kummer F. The action of a tropic acid ester on bronchospasm:A double-blind study [Zur wirkung eines tropasaure-esters auf den bronchospasmus]. Wiener Klinische Wochenschrift 1975; 87(4):132-6. - PubMed
Brown 1984 {Published data only}
Dejaegher 1984 {Published data only}
-
- Dejaegher Ph, Demedts M, Rochette F, Van der Veken J. Effects of 40ug and 400ug of ipratropium bromide in obstructive lung disease. Acta Clinica Belgica 1984; 39(3):136-40. - PubMed
Disse 1999 {Published data only}
-
- Disse B, Speck GA, Rominger KL, Witek TJ, Hammer R. Tiotropium (SPIRIVA): Mechanistical considerations and clinical profile in obstructive lung disease. Life Sciences 1999; 64(6/7):457-64. - PubMed
Heimer 1991 {Published data only}
-
- Heimer D, Brami JL, Liberman D, Bark H. Comparison of a B2 adrenergic agonist and an anticholinergic agent given by sequential inhalation in patients with severe chronic obstructive pulmonary disease. Israel Journal of Medical Science 1991; 27:307-10. - PubMed
Hidalgo 1983 {Published data only}
-
- Banos Hidalgo P, Ramos Martos A, Cabrera Moreno R, Luque Leal J, Palcios Giner YA. Comparacion en estudio doble ciego de la asociacion de un aerosol de salbutamol y bromuro de ipratropio y de su efecto individual en bronquitis cronica y asma bronquial. Revista Clinica Espanola 1983; 171(4):265-8. - PubMed
Kheir 1993 {Published data only}
-
- Kheir A, Ying Y, Hannhart B, Duvivier C, Peslin R, Polu JM. Comparison de l'effet bronchodilatateur at du site d'action du fenoterol et de l'ipratropium chez bronchiteux chroniques obstructifs [A comparison of the bronchodilator effect and the site of action of fenoterol and of ipratropium in bronchitis with airflow obstruction]. Revue des Maladies Respiratoires 1993; 10:9-15. - PubMed
Khristoliubova 1999 {Published data only}
-
- Khristoliubova EI, Volkova LI, Shcherbakova IV. Long-term atrovent treatment of chronic obstructive bronchitis. Klinicheskaia Meditsina (Mosk) 1999; 77(12):51-2. - PubMed
Lees 1980 {Published data only}
-
- Lees AW, Allan GW, Smith J. Nebulised ipratropium bromide and salbutamol in chronic bronchitis. British Journal of Clinical Practise 1980; 34(11-12):340-2. - PubMed
Leitch 1978 {Published data only}
Lien 1980 {Published data only}
-
- Lien J Th. Clinical comparison of Atrovent and placebo in patients with chronic obstructive lung diseases [Klinisk sammenligning av Atrovent og placebo hos pasienter med kronisk ostruktiv lungesykdom]. Tidsskr Nor Loegeforen 1980; 100(19-21):1193-5. - PubMed
Matera 1996 {Published data only}
-
- Matera MG, Caputi M, Cazzola M. A combination with clinical recommended dosages of salmeterol and ipratropium is not more effective than salmeterol alone in patients with chronic obstructive pulmonary disease. Respiratory Medicine 1996; 90:497-9. - PubMed
Nardini 1996 {Published data only}
-
- Nardini S. Inhaled antimuscarinic agents and COPD. Monaldi Archives for Chest Disease 1996; 51(1):52-3. - PubMed
Nishimura 1992 {Published data only}
-
- Nishimura K, Koyama H, Izumi T. A comparison of bronchodilating drugs for the treatment of stable COPD. Nihon Hyobu Shikkan Gakkai Zasshi 1992; 30(5):835-43. - PubMed
Petro 1981 {Published data only}
-
- Petro W, Nakhosteen JA, Konietzko N. Bronchodilator effect of a combination of a beta-adrenergic agonist and a cholinergic antagonist [Broncholyse unter kombinierter anwendung von Beta-adrenergen agonisten und cholinergen antagonisten]. Praxis der Pneumologie vereinigt mit Der Tuberkuloserarzt 1981; 35:779-82.
Pierce 1982 {Published data only}
-
- Pierce RJ, Holmes PW, Campbell AH. Use of ipratropium bromide in pateints with severe airways obstruction. Australian and New Zealand Journal of Medicine 1982; 12:38-43. - PubMed
Shmelev 1999 {Published data only}
-
- Shmelev EI, Khmel'kova NG, Nonikov DV, Melent'eva EM, Abubikirov AF, Makarova VL, et al. Experience in long-term use of berodual in the treatment of patients with chronic obstructive bronchitis. Terapevticheskii Arkhiv 1999; 71(3):22-4. - PubMed
Simanenkov 1998 {Published data only}
-
- Simanenkov VI, Il'iashevich IG, Liparteliani BG, Ledovaia AV. Long-term atrovent treatment of chronic obstructive bronchitis [Dlitel'noe lechenie atroventom pri khronicheskom obstruktivnom bronkhite]. Terapevticheskii Arkhiv 1998; 70(9):77-9. - PubMed
Tang 1984 {Published data only}
-
- Tang OT, Flatley M. A comparison of effects of inhaling a combined preparation of fenoterol with ipratropium bromide (Duovent) with those of fenoterol and salbutamol. Postgraduate Medical Journal 1984; 60:24-7. - PubMed
Additional references
Anthonisen 1986
-
- Anthonisen NR, Wright EC. Bronchodilator response in chronic obstructive pulmonary disease. American Review of Respiratory Disease 1986; 133:814-9. - PubMed
Anthonisen 1994
-
- Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: The Lung Health Study. JAMA 1994; 272:1497-505. - PubMed
Appleton 2001
-
- Appleton S, Poole P, Smith B, Cates C, Veale A, Bara A. Long-acting beta2-agonists for chronic obstructive pulmonary disease patients with poorly reversible airflow limitation (Cochrane review). The Cochrane Database of Systematic Reviews 2001, Issue 4. - PubMed
Appleton 2006
ATS/ERS 2004
-
- Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. European Respiratory Journal 2004; 23:932-46. - PubMed
Barnes 1993
-
- Barnes PJ. Theoretical aspects of anticholinergic treatment. In: Gross NJ, editors(s). Anticholinergic therapy in obstructive airways disease. London: Franlkin Scientific Publications, 1993.
Barr 2005
Belman 1996
-
- Belman M, Botnick W, Shin J. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. American Journal of Respiratory & Critical Care Medicine 1996; 153:967-75. - PubMed
Blosser 1995
-
- Blosser SA, Maxwell SL, Reeves-Hoche MK, Localio AR, Zwillich CW. Is an anti-cholinergic agent superior to a beta-2 agonist in improving dyspnea and exercise limitation in COPD? Chest 1995; 108:730-5. - PubMed
Boyd 1997
-
- Boyd G, Morice AH, Pounsford JC, Siebert M, Peslis N, Crawford C. An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD). European Respiratory Journal 1997; 10:815-21. - PubMed
BTS 1997
Calverly 2003
Chapman 1991
-
- Chapman KR. Clinical implications of anticholinergic bronchodilator therapy in COPD. Research & Clinical Forums 1991; 13(2):43-50.
Cwealth of Aust 2000
-
- Commonwealth of Australia. Schedule of Pharmaceutical Benefits Effective from May 2001; GENERAL Respiratory system. http://www.health.gov.au/pbs/scripts/dispgp.cfm 2000.
D'Urzo 2001
-
- D'Urzo A, De Salvo M, Ramirez-Rivera A, Almeida J, Sichletidis L, Rapatz G, Kottakis J. In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium: A 3 week, randomized, double-blind, with-in patient, multicentre study. Chest 2001; 119:1347-56. - PubMed
Ferguson 2000
-
- Ferguson G. Recommendations for the management of COPD. Chest 2000; 117(2 Suppl):23s-28s. - PubMed
GOLD 2003
-
- National Heart, Lung, and Blood Institute. Global Initiative on Obstructive Lung Disease (GOLD) Pocket Guide (updated 2003). www.goldcopd.com [accessed 16/02/04].
GOLD 2004
-
- National Heart, Lung, and Blood Institute. Global Initiative for Chronic Obstructive Pulmonary Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (Updated 2004). www.goldcopd.com [accessed 21/03/05].
Jadad 1996
-
- Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clinical Trials 1996; 17(1):1-12. - PubMed
Mahler 2002
-
- Mahler DA, Wire P, Horstman D, Chang CN, Yates J, Fischer T, et al. Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease. American Journal of Respiratory & Critical Care Medicine 2002; 166:1084-91. - PubMed
Matera 1995
-
- Matera MG, Cazzola M, Vinciguerraaa A, et al. Comparison of hte bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease. Pulmonary Pharmacology 1995; 8:267-71. - PubMed
NICE/BTS 2004
Nisar 1992
-
- Nisar M, Earis JE, Pearson MG, Calverly PMA. Acute bronchodilator trials in chronic obstructive pulmonary disease. American Review of Respiratory Disease 1992; 146:555-9. - PubMed
O'Donnell 1997
-
- O'Donnell D, Bertley J, Chau L, Webb K. Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiological mechanisms. American Journal of Respiratory & Critical Care Medicine 1997; 155:109-15. - PubMed
O'Donnell 1998
-
- O'Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation and endurance during exercise in chronic obstructive pulmonary disease. American Journal of Respiratory & Critical Care Medicine 1998; 158:1557-65. - PubMed
O'Donnell 1999
-
- O' Donnell D, Lam M, Webb K. Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. American Journal of Respiratory & Critical Care Medicine 1999; 160:542-9. - PubMed
O'Donnell 2000
-
- O' Donnell D. Assessment of bronchodilator efficacy in symptomatic COPD. Is spirometry useful? Chest 2000; 117(2 Suppl):42s-47s. - PubMed
Pauwels 2000
-
- Pauwels R. National and international guidelines for COPD: The need for evidence. Chest 2000; 117(2 Suppl):20s-22s. - PubMed
Rossi 2002
-
- Rossi A, Kristufek P, Levine BE, Thomson MH, Till D, Kottakis J, et al. Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD. Chest 2002; 121:1058-69. - PubMed
Spencer 2004
-
- Spencer S, Calverley PM, Burge PS, Jones PW. Impact of preventing exacerbations on deterioration of health status in COPD. European Respiratory Journal 2004; 23(5):698-702. - PubMed
Tashkin 2003
-
- Tashkin D, Kesten S. Long-term treatment benefits with tiotropium in COPD patients with and without short-term bronchodilator responses. Chest 2003; 123:1441-49. - PubMed
Ullah 1981
Ulrik 1995
van Weel 1998
-
- Weel C. Combining nebulised ipratropium and albuterol improved FEV1 but did not improve symptoms or quality of life in COPD. Evidence-Based Medicine 1998:120.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous