Authors' objectives:

The aim of this report was to critically examine the clinical effectiveness, through a systematic review of the literature, of inhaled long-acting beta2-agonists in patients with stable chronic obstructive pulmonary disease (COPD) and reversible or non-reversible airway obstruction by addressing the following two research questions:

1. What is the effectiveness of inhaled long-acting beta2-agonists versus inhaled anticholinergics (ipratropium and tiotropium), with or without short-acting beta2-agonist aerosol agents taken on an as-needed basis?

2. What is the effectiveness of inhaled long-acting beta2-agonists versus placebo, with or without short-acting beta2-agonist aerosol agents taken on an as-needed basis?

Authors' results and conclusions: Of the 150 potentially relevant reports identified, 54 summarizing the results of 33 unique RCTs satisfied the inclusion criteria for this review. Of these, 20 trials compared salmeterol and placebo; two compared salmeterol, ipratropium bromide, and placebo; two compared salmeterol, tiotropium; and placebo; and one compared salmeterol and tiotropium. Five RCTs compared formoterol and placebo; two compared formoterol, ipratropium, and placebo; and one compared formoterol and tiotropium. Overall, more robust data were available for salmeterol than formoterol. Based on the Jadad scale, the quality assessment of these trials showed that 21 (64%) were of higher quality (quality score >3 or =3) and 12 (36%) were of lower quality (quality scores of 1 to 2). Higher quality studies are associated with less exaggerated estimates of effectiveness. No significant differences were observed between long-acting beta2-agonists and ipratropium bromide or tiotropium in the outcome measures assessed, with the exception of symptom-free days. For this outcome measure, one study reported a significant advantage of formoterol over ipratropium, and better improvement in lung function with tiotropium over salmeterol (FVC) and formoterol (FEV1), but this was not supported by other evidence. Based on two studies, withdrawal due to adverse events occurred more often in salmeterol recipients compared with tiotropium recipients [odds ratio (OR) 2.16, 95% confidence interval (CI): 1.36 to 3.43]. Compared with placebo, long-acting beta2-agonists reduced COPD exacerbations [OR 0.74 (95% CI: 0.64; 0.87)] and hospitalizations [OR 0.62 (95% CI: 0.40; 0.96)]. Most studies indicate that long-acting beta2-agonists are better than placebo in reducing the use of rescue inhalers, and improving the number of symptom-free days, the level of dyspnea, and the measures of lung function (FEV1, FVC, peak expiratory flows). Their effect on measures of quality of life was inconsistent across studies. Long-acting beta2-agonists did not demonstrate detectable differences on mortality, withdrawals due to adverse events, URTIs, or exercise capacity as measured by the walk test, compared with placebo.

Authors' recommendations: Long-acting beta2-agonists were significantly more effective than placebo in reducing COPD exacerbations and hospitalizations. Improvement in the use of rescue inhalers, symptom-free days, dyspnea, and lung function were also observed, although confirmation through further study may be required. Long-acting beta2-agonists did not have any significant advantages over placebo in reducing mortality and upper respiratory tract infections, or improving exercise capacity and tolerability. Long-acting beta2-agonists did not demonstrate a significant advantage compared with either anticholinergic agent in most functional outcome measures. Salmeterol is not as well tolerated as tiotropium. No data were available to compare the tolerability of formoterol with tiotropium.

Authors' methods: Overview

Project Status: Completed

URL for project: https://www.ccohta.ca/

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Canadian Coordinating Office for Health Technology Assessment

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553, Fax: +1 613 226 5392;

Contact Name: requests@cadth.ca

Contact Email: requests@cadth.ca

Copyright: Canadian Coordinating Office for Health Technology Assessment (CCOHTA)