TORCH and UPLIFT: what has been learned from the COPD "mega-trials"?

Abstract

TORCH and UPLIFT are amongst the largest and most ambitious COPD trials ever undertaken. In terms of the primary outcomes, both trials were negative. Compared with placebo, combined salmeterol and fluticasone therapy did not significantly reduce all cause mortality over 3 years in TORCH, and tiotropium did not slow the decline in lung function over 4 years in UPLIFT. Secondary outcomes from these studies strongly confirmed findings from previous trials. Monotherapy with all three drugs provided small improvements in respiratory health status and reductions in exacerbation rates with some additive effect from the salmeterol/fluticasone combination. Both salmeterol/fluticasone and tiotropium also reduced COPD hospitalization rates. The trials provide very strong evidence that the long-acting bronchodilators, salmeterol and tiotropium, are not associated with increased risk of death or major cardiovascular adverse events.