Long-acting beta2-agonists for chronic obstructive pulmonary disease patients with poorly reversible airflow limitation

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterised by partially reversible airflow limitation. Many patients have little reversibility to short acting bronchodilators, but long acting bronchodilators are frequently advocated.

Objectives: To determine the effectiveness of long acting beta-2 adrenoceptor agonists in COPD patients with low reversibility to short-acting bronchodilators.

Search strategy: The Cochrane Airways Group register was searched. Bibliographies of identified randomised controlled trials (RCTs) were also searched. Authors of identified RCTs were contacted for other published and unpublished studies and unpublished studies were obtained from pharmaceutical companies.

Selection criteria: All RCTs over four weeks in duration comparing treatment with long-acting beta-2 adrenoceptor agonists (salmeterol or formoterol) with placebo in patients with stable poorly-reversible COPD.

Data collection and analysis: Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data were required, authors of studies were contacted.

Main results: Eight RCTs met the inclusion criteria review. Six were parallel group studies of 12-16 weeks in duration and two were cross-over studies with four week treatment arms. All eight assessed the efficacy of salmeterol in COPD compared to placebo. Few of the results could be combined in meta-analyses because of differences in methods of reporting data. Isolated trials reported an improvement in one or other outcome in favour of salmeterol, but the only possible meta-analysis of FEV1 showed no overall benefit (Standardised mean difference 0.14 (95% Confidence Interval -0.16, 0.44, n=4). There was no consistent effect on Health Related Quality of LIfe or symptoms scores. Overall, breathlessness was not reduced, but in one study more subjects in the salmeterol group had low Borg dyspnoea scores compared to placebo (Peto Odds Ratio = 0.60, 95% CI: 0.40; 0.88). There was no effect on COPD exacerbations over the short period of the studies.

Reviewer's conclusions: In the few studies that could be included in this review, treatment of patients with COPD with long acting beta-2 agonists produces only small increases in FEV1. The improvement in airways function does not seem to be associated with a consistent effect on other outcomes such as health related quality of life or reductions in breathlessness.