Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial

Background: Inhaled longacting β2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone. Methods: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 μg salmeterol twice daily (n=372), 500 μg fluticasone twice daily (n=374), 50 μg salmeterol and 500 μg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1 s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12 h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol. Findings: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p