O1.2.2 Long-acting beta-agonists

Long-acting beta-agonists cause prolonged bronchodilatation and can be administered once (indacaterol) or twice daily (salmeterol, eformoterol). A systematic review of randomised controlled trials (Appleton et al., 2006b) found that compared to placebo, long-acting beta-agonists used for at least four weeks produce statistically significant benefits in lung function, quality of life, use of ‘reliever’ short-acting bronchodilators and acute exacerbations. This review compared different drugs and doses independently, the commonest being salmeterol 50 mcg daily which involved up to 3363 participants. It would be necessary to treat 24 (95% CI 14 to 98) patients with salmeterol to prevent one exacerbation.

The review did not find evidence that higher doses of salmeterol were more beneficial than 50mcg/day. Fewer studies of the effect of eformoterol were included and they were not combined in a meta-analysis, but some benefits similar to those of salmeterol were seen for a range of outcomes across a range of doses. Adverse drug effects were not reported.

Indacaterol is an inhaled ultra long-acting beta₂ agonist that can be given as a once daily maintenance therapy for COPD. Compared to placebo, indacaterol improves FEV₁, dyspnoea and health-related quality of life, and reduces exacarbations (Dahl et al., 2010), (Donohue et al., 2010), (Chapman et al., 2011), (Jones et al., 2011b), (Kornmann et al., 2011) [evidence level II]. The long-term bronchodilator effects of indacaterol are at least as good as tiotropium (Donohue et al., 2010), formoterol (Dahl et al., 2010) or salmeterol. (Kornmann et al., 2011)

The efficacy of long-acting beta-agonists compared to ipratropium bromide alone, or in combination, have also been combined in a systematic review. (Appleton et al., 2006a) Comparisons of monotherapy found a greater increase in FEV₁, weighted mean difference = 60 mls (95% CI 0 to 110), and morning PEF, weighted mean difference = 10.96 l/min (95% CI 5.83 to 16.09) for salmeterol over ipratropium bromide. There were no significant differences between interventions for quality of life, functional capacity, symptoms, acute exacerbations or adverse events. Comparisons of the combination of ipratropium bromide and salmeterol with ipratropium bromide alone showed varying effects on lung function and symptoms, but a small, significant reduction in reliever use; weighted mean difference = -0.67 puffs/day (95% CI -1.11 to -0.23).