Effect of Pharmacotherapy on Rate of Decline of Lung Function in Chronic Obstructive Pulmonary Disease

Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function. No drug has been shown conclusively to reduce this decline. Objectives: In a post hoc analysis of the Toward a Revolution in COPD Health (TORCH) study, we investigated the effects of combined salmeterol 50 μg plus fluticasone propionate 500 μg, either component alone or placebo, on the rate of post-bronchodilator FEV₁ decline in patients with moderate or severe COPD. Methods: A randomized, double-blind, placebo-controlled study was conducted from September 2000 to November 2005 in 42 countries. Of 6,112 patients from the efficacy population, 5,343 were included in this analysis. Measurements and Main Results: Spirometry was measured every 24 weeks for 3 years. There were 26,539 on-treatment observations. The adjusted rate of decline in FEV₁ was 55 ml/year for placebo, 42 ml/year for salmeterol, 42 ml/year for fluticasone propionate, and 39 ml/year for salmeterol plus fluticasone propionate. Salmeterol plus fluticasone propionate reduced the rate of FEV₁ decline by 16 ml/year compared with placebo (95% confidence interval [CI], 7–25; P < 0.001). The difference was smaller for fluticasone propionate and salmeterol compared with placebo (13 ml/year; 95% CI, 5–22; P = 0.003). Rates of decline were similar among the active treatment arms. FEV₁ declined faster in current smokers and patients with a lower body mass index, and varied between world regions. Patients who exacerbated more frequently had a faster FEV₁ decline. Conclusions: Pharmacotherapy with salmeterol plus fluticasone propionate, or the components, reduces the rate of decline of FEV₁ in patients with moderate-to-severe COPD, thus slowing disease progression. Clinical trial (GSK Study Code SCO30003) registered with www.clinicaltrials.gov (NCT00268216).