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

Background Inhaled longacting beta(2) 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 mug salmeterol twice daily (n=372), 500 mug fluticasone twice daily (n=374), 50 mug salmeterol and 500 mug 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 6 h 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<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration. Interpretation Because inhaled long-acting beta(2) agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.