Introduction: Concerns have been raised regarding the safety of extended use of long-acting beta2-agonists (LABAs). The safety of arformoterol (50 microg QD), and salmeterol (42 microg BID), was assessed over 12 months in subjects with COPD. The study also examined the occurrence of tolerance with these agents, i.e. whether improvement in airway function diminished or frequency of exacerbations increased with 12-months of use.
Methods: Subjects with COPD (mean FEV1 1.2 L, ~41% predicted) were enrolled in the study and randomized to receive nebulized arformoterol 50 microg QD (n = 528) or salmeterol 42 microg BID (MDI; n = 265) in a prospective, multicenter, open-label, 12-month trial. The frequency of adverse events, COPD exacerbations, and use of short-acting bronchodilator agents were assessed throughout the study period. Pulmonary function was also examined.
Results: Among treated subjects, the frequency of adverse events was similar for those taking arformoterol (90.5%) and salmeterol (88.3%). Tremor was more frequent among subjects treated with arformoterol (13.4%) than those treated with salmeterol (1.1%). The frequency of COPD exacerbations did not increase over 12 months for arformoterol and salmeterol (weeks 0-13: 15.7% and 11.7%, respectively; weeks 39-52: 10.0% and 9.4%, respectively). Supplemental ipratropium bromide and rescue racemic albuterol use decreased for both groups by 0.8 to 1.5 actuations/day, decreases that remained stable throughout the 52-week study. Mean predose (trough) FEV1 improved for arformoterol and salmeterol at week 13 (7.1% +/- 17.0 and 7.6% +/- 17.8, respectively) and the improvement continued at week 52 (5.9% and 6.2%, respectively). Mean peak percent predicted postdose FEV1 over the course of the 52-week study declined by about 2% for both treatments, but throughout was higher for arformoterol than for salmeterol.
Conclusion: In this trial, both arformoterol 50 microg QD and salmeterol 42 microg BID were well tolerated in patients with COPD. Both LABAs produced effective bronchodilation and their use was not associated with the development of clinically meaningful tolerance over a 1-year treatment period.