Peter M A Calverley1,2, Julie A Anderson3, Robert D Brook4, Courtney Crim5, Natacha Gallot6, Sally Kilbride3, Fernando J Martinez4,7, Julie Yates5, David E Newby8, Jørgen Vestbo9, Robert Wise10, Bartolomé R Celli11. 1. 1 Department of Medicine, University of Liverpool, Liverpool, United Kingdom. 2. 2 Clinical Sciences Centre, University Hospital Aintree, Liverpool, United Kingdom. 3. 3 Research & Development, GlaxoSmithKline, Stockley Park, United Kingdom. 4. 4 University of Michigan Health System, Ann Arbor, Michigan. 5. 5 Research & Development, GlaxoSmithKline, Research Triangle Park, North Carolina. 6. 6 Veramed Ltd., Twickenham, United Kingdom. 7. 7 Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, New York. 8. 8 Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. 9. 9 Division of Infection, Immunity and Respiratory Medicine, Manchester Academic Health Sciences Centre, The University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester, United Kingdom. 10. 10 Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medicine, Baltimore, Maryland; and. 11. 11 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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 β-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).
RCT Entities:
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 β-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).
Entities:
Keywords:
COPD; fluticasone furoate; rate of decline in FEV1; vilanterol
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