THE TOWARDS A REVOLUTION IN COPD HEALTH (TORCH) STUDY: FLUTICASONE PROPIONATE/SALMETEROL IMPROVES SURVIVAL IN COPD OVER THREE YEARS

Abstract

PURPOSE: COPD is the only major chronic cause of death that is increasing globally. Our objective was to investigate whether salmeterol (SAL) and fluticasone propionate (FP) combined in a single formulation (FSC) could significantly impact survival. METHODS: 6112 (intention to treat population) patients with moderate to severe COPD (<60% predicted FEV1) from 42 countries (mean age 65yrs, 76% males, 44% predicted post-bronchodilator FEV1; 3.7% reversibility to albuterol as % of predicted, 43% current smokers) were randomised to receive FP 500mcg (n=1534), SAL 50mcg (n=1521), FSC 500/50 (n=1533), or placebo (n=1524) bid via Diskus(R)in a 3 year double-blind study. Two interim analyses were carried out by an independent data monitoring board. The primary analysis was log-rank analysis of time to all-cause mortality (FSC vs placebo) at 156 weeks. RESULTS: FSC reduced the risk of dying at any time by 18% compared with placebo (HR 0.825, 95% CI 0.68-1.00; p=0.052 adjusted for interim analyses; absolute rates 15.2% vs 12.6%; absolute reduction 2.6%). Supportive secondary analysis confirmed the result (Cox's proportional hazards: HR 0.811, 95% CI 0.67-0.98; p=0.031). Component arms were not significantly different from placebo (SAL HR 0.88, 95% CI 0.73-1.06; FP HR 1.06, 95% CI 0.89-1.27). There was also a trend to reduction in COPD-related mortality with FSC vs placebo (6.0% vs 4.7%, HR 0.78, 95% CI 0.57-1.06; p=0.107). No significant interaction with baseline FEV1 by GOLD stage was found (<30%, 30-50% and >50%; p= 0.402). Further, there were no interactions by smoking status, age, sex or BMI (all p>0.12). CONCLUSION: FSC improves survival in this population of patients with COPD vs placebo over 3 years. This effect was not seen with the components alone.