Combination therapy with fluticasone plus salmeterol was associated with reduced mortality, but the difference was just short of statistical significance.
It is unclear whether inhaled corticosteroids and long-acting ß-agonists reduce mortality in patients with chronic obstructive pulmonary disease. In this industry-sponsored international trial (known as TORCH), researchers randomized more than 6000 COPD patients to receive inhaled salmeterol plus fluticasone (Advair 50/500), salmeterol (Serevent) alone, fluticasone (Flovent) alone, or placebo — all given twice daily. Enrollment criteria included a history of smoking, FEV1 <60% of predicted, and reversibility with albuterol that was less than 10% of the patient's predicted FEV1.
At 3 years, the following outcomes were noted:
All-cause mortality (the primary endpoint) was 12.6% with combined therapy, 13.5% with salmeterol, 16.0% with fluticasone, and 15.2% with placebo. The difference between combined therapy and placebo did not quite reach significance (P=0.052).
Combined therapy and salmeterol alone, but not fluticasone alone, significantly reduced the rate of hospitalization for COPD exacerbation.
Pneumonia occurred more frequently in the two groups receiving fluticasone (about 19%) than in the placebo or salmeterol-alone groups (about 13%).
Combined therapy was superior to both monotherapies — which, in turn, were superior to placebo — in reducing the number of moderate or severe COPD exacerbations and in mitigating the declines in FEV1 and health status scores.
Comment: In this study of COPD patients, inhaled therapy with fluticasone plus salmeterol was associated with a 2.6 percentage-point reduction in mortality that just failed to reach statistical significance. In several respects, salmeterol monotherapy appeared superior to fluticasone monotherapy — an interesting outcome given the current controversy about potential harms with long-acting ß-agonists in asthma. How to interpret this trial will be debated for some time; for now, an editorialist concludes that combination therapy offers several advantages (but not clear-cut mortality reduction), that steroid monotherapy "should not be advocated," that salmeterol monotherapy "appears to be safe," and that the increased incidence of pneumonia with fluticasone requires further investigation.
— Allan S. Brett, MD
Published in Journal Watch General Medicine February 21, 2007
Calverley PMA et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007 Feb 22; 356:775-89.