Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids are used to treat chronic obstructive pulmonary disease (COPD), but their effect on survival is unknown. METHODS: We conducted a randomized, double-blind trial comparing salmeterol at a dose of 50 μg plus fluticasone propionate at a dose of 500 μg twice daily (combination regimen), administered with a single inhaler, with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. The primary outcome was death from any cause for the comparison between the combination regimen and placebo; the frequency of exacerbations, health status, and spirometric values were also assessed. RESULTS: Of 6112 patients in the efficacy population, 875 died within 3 years after the start of the study treatment. All-cause mortality rates were 12.6% in the combinationtherapy group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 16.0% in the fluticasone group. The hazard ratio for death in the combination-therapy group, as compared with the placebo group, was 0.825 (95% confidence interval [CI], 0.681 to 1.002; P = 0.052, adjusted for the interim analyses), corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo. As compared with placebo, the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values (P