Rebuttal: Should we avoid β-agonists for moderate and severe chronic obstructive pulmonary disease?

Dr Aaron has accurately outlined the beneficial effects of β-agonist use on lung function in patients with chronic obstructive pulmonary disease (COPD). It is important to point out that anticholinergic agents, such as ipratropium and tiotropium, are equally effective bronchodilators for COPD. Anticholinergics, however, have been shown to reduce respiratory mortality substantially compared with placebo, while some evidence suggests that β-agonists might actually increase respiratory mortality. In our recent meta-analysis we pooled all the data on respiratory deaths available to us at the time, after contacting the investigators of the trials to obtain unpublished information. When a subsequent letter to the editor reported that duplicate data had been provided for 2 of the published trials, we reanalyzed the data with the duplicate data excluded, and there was still a statistically significant twofold increase in respiratory mortality for βagonists compared with placebo.¹

The TORCH (Towards a Revolution in COPD Health) trial has recently been published,² and it is true that it showed a nonsignificant trend toward reduced total mortality in the salmeterol group compared with the placebo group. Dr Aaron failed to note, however, that there was actually an increase in COPD deaths and respiratory deaths in the salmeterol group compared with the placebo group, although this did not reach statistical significance. If the TORCH data were added to the pooled data on β-agonist use for COPD, there would still be an increase in respiratory mortality for β-agonists compared with placebo, although the results might not reach statistical significance any more. This is in stark contrast with the pooled data on anticholinergic agents that show a statistically significant 70% (P = .02) reduction in respiratory deaths compared with placebo.³ Trials that have directly compared the 2 types of bronchodilators have shown a statistically significant fivefold increase in total mortality with β-agonists compared with anti-cholinergics.⁴ This indicates that anticholinergic agents should be the drugs of choice to achieve safe and effective bronchodilation for patients with COPD.