Fluticasone Furoate, Vilanterol, and Lung Function Decline in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk.

ABSTRACT

RATIONALE Many patients with chronic obstructive pulmonary disease (COPD) have an accelerated loss of lung function. It is unclear whether drug treatment can modify this in patients with moderately severe disease. OBJECTIVES: In a prespecified analysis of the key secondary outcome in SUMMIT (Study to Understand Mortality and Morbidity), we investigated whether the inhaled corticosteroid fluticasone furoate (FF; 100 µg), the long-acting ß-agonist vilanterol (VI; 25 µg), or their combination (FF/VI) modified the rate of decline in FEV1 compared with placebo. We also investigated how baseline covariates affected this decline. METHODS: Spirometry was measured every 12 weeks in this event-driven, randomized, placebo-controlled trial of 16,485 patients with moderate COPD and heightened cardiovascular risk. An average of seven spirometric assessments per subject among the 15,457 patients with at least one on-treatment measurement were used in the analysis of rate of FEV1 decline. All statistical comparisons are considered nominal. MEASUREMENTS AND MAIN RESULTS: The adjusted rates of FEV1 decline were -46 ml/yr (-3.0% of baseline) with placebo, -47 ml/yr (-3.1%) with VI, -38 ml/yr (-2.5%) with FF, and -38 ml/yr (-2.3%) with FF/VI. FF-containing regimens had lower rates of decline than placebo (P < 0.03), and FF/VI had a lower rate of decline than VI alone (P < 0.005). The FEV1 decline was faster in current smokers, those with a lower body mass index, males, and patients with established cardiovascular disease. CONCLUSIONS: In patients with moderate COPD and heightened cardiovascular risk, FF alone or in combination with VI appears to reduce the rate of FEV1 decline. Clinical trial registered with www.clinicaltrials.gov (NCT01313676).