Combining classes of bronchodilators may have additive effects in COPD treatment. We evaluated the effectiveness of adding the long-acting beta agonist, arformoterol, to maintenance therapy with the long-acting anticholinergic, tiotropium.
This was a single-center, double-blinded, crossover study in clinically-stable COPD patients. All received open-label inhaled tiotropium (18 mcg) daily throughout the 5-week study. After a 2 week run-in, patients were randomized to also receive via nebulizer, either arformoterol (15 mcg) or placebo twice daily for 1 week. After a 1-week washout, they crossed over to the opposite arm. Outcome variables included forced expiratory volume in 1-second (FEV1), treadmill endurance time at 80% of maximum, and inspiratory capacity (IC) at rest and at iso-time during exercise. The FEV1 and static IC were measured at baseline (trough) and 2 hours after drug administration. Exercise testing was done immediately after the second spirometry.
Twenty patients were studied; their mean age was 68 ± 9 years, and FEV1 was 53 ± 9%. The mean changes in FEV1 and static IC two hours after open-label tiotropium administration were 104 ± 26 mL (SE) (p < 0.001) and 77 ± 43 mL (p = 0.09), respectively. The additive FEV1 trough and peak effects of arformoterol were 69 ± 48 mL (p = 0.17) and 121 ± 37 mL (p = 004); peak tiotropium-arformoterol resulted in a 225 ± 46 mL increase over tiotropium trough (p < 0.001). Adding arformoterol to tiotropium resulted in a 113 ± 63 mL further increase in IC (p = 0.09). There were no significant between-group differences in exercise endurance time or iso-time IC.
Adding the long-acting beta agonist arformoterol to maintenance tiotropium therapy resulted in additional improvement in lung function, but not exercise capacity or dynamic hyperinflation in COPD patients.
This preliminary, proof of concept study demonstrated that adding arformoterol to tiotropium further improved lung function in COPD patients. The study was probably underpowered to detect changes in exercise variables.
Binusha Moitheennazima, Grant monies (from industry related sources) This investigator-initiated study was funded by Sepracor, Inc.; No Product/Research Disclosure Information