Commentary

Current guidelines recommend that an anticholinergic agent be combined with a β₂ adrenergic agonist when inhaled bronchodilator treatment is prescribed for patients with severe or exacerbated COPD. Short acting anticholinergics and short acting β₂ agonists produce similar bronchodilation in patients with stable COPD.¹ Combined treatment produces larger FEV₁ increases than does either agent alone, but the additive effect is modest and the clinical benefit remains uncertain.¹

The meta-analysis by McCrory and Brown shows that anticholinergics and short acting β₂ agonists are similar also when given alone to patients admitted to hospital for COPD exacerbations. However, combined treatment seems to provide no additive bronchodilation during exacerbation, either short (90 mins) or longer term (24 h).

Several reasons are possible for this seeming disparity, although none are readily apparent. Chance can never be fully excluded. Although several hundred patients are included in the meta-analysis, there is a small possibility that FEV₁ differences as large as 100 ml might not have been detected, and changes of this magnitude during exacerbation seem to be clinically meaningful.²

None of the trials included in the meta-analysis attempted to evaluate clinical outcomes. McCrory and Brown suggest the need for a very large trial to better evaluate patient oriented endpoints, but it is doubtful that support will ever be found for such a large, expensive project. Hence, treatment recommendations will continue to be made from the available evidence, which provides little justification for combining an anticholinergic with a β₂ agonist in the treatment of COPD exacerbations. As monotherapy, the 2 drug classes seem to be equally effective, and because both have excellent safety profiles, individual patient preference or cost should dictate the choice.