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