Fernando J Martinez1,2, Jørgen Vestbo3, Julie A Anderson4, Robert D Brook2, Bartolome R Celli5, Nicholas J Cowans6, Courtney Crim7, Mark Dransfield8, Sally Kilbride4, Julie Yates7, David E Newby9, Dennis Niewoehner10, Peter M A Calverley11. 1. 1 Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, New York. 2. 2 University of Michigan Health System, Ann Arbor, Michigan. 3. 3 Division of Infection, Immunity and Respiratory Medicine, Manchester Academic Health Sciences Centre, The University of Manchester and South Manchester, Manchester, United Kingdom. 4. 4 Research & Development, GlaxoSmithKline, Stockley Park, Middlesex, United Kingdom. 5. 5 Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 6. 6 Veramed Ltd., Twickenham, United Kingdom. 7. 7 Research & Development, GlaxoSmithKline, Research Triangle Park, North Carolina. 8. 8 University of Alabama Birmingham, Birmingham, Alabama. 9. 9 Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. 10. 10 University of Minnesota, Minneapolis, Minnesota; and. 11. 11 University of Liverpool, Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, United Kingdom.
Abstract
RATIONALE: Inhaled corticosteroids have been shown to decrease exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Their effects in patients with milder airflow obstruction remain unclear. OBJECTIVES: This was an analysis of exacerbations in the SUMMIT (Study to Understand Mortality and Morbidity) study. METHODS: In a double-blind, randomized controlled trial, once-daily inhaled placebo, fluticasone furoate (FF; 100 μg), vilanterol (VI; 25 μg), or the combination of FF/VI was administered. The primary outcome was all-cause mortality. Exacerbations of COPD were an additional predefined endpoint. A total of 1,368 centers in 43 countries and 16,485 patients with moderate COPD and heightened cardiovascular risk were included in the study. MEASUREMENTS AND MAIN RESULTS: Compared with placebo, FF/VI reduced the rate of moderate and/or severe exacerbations by 29% (95% confidence interval [CI], 22-35; P < 0.001) and the rate of hospitalized exacerbations by 27% (95% CI, 13-39; P < 0.001). These relative effects were similar regardless of whether subjects had a history of exacerbation in the year before the study or an FEV1 <60% or ≥60% of predicted. The number needed to treat was not influenced by baseline FEV1 but was influenced by the history of exacerbations. FF/VI also reduced the rate of exacerbations treated with corticosteroids alone or with corticosteroids and antibiotics but not the rates of those treated with antibiotics alone. CONCLUSIONS:Patients with moderate chronic airflow obstruction experienced a reduction in exacerbations with FF/VI compared with placebo, irrespective of a history of exacerbations or baseline FEV1. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676; GSK Study number 113782).
RCT Entities:
RATIONALE: Inhaled corticosteroids have been shown to decrease exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Their effects in patients with milder airflow obstruction remain unclear. OBJECTIVES: This was an analysis of exacerbations in the SUMMIT (Study to Understand Mortality and Morbidity) study. METHODS: In a double-blind, randomized controlled trial, once-daily inhaled placebo, fluticasone furoate (FF; 100 μg), vilanterol (VI; 25 μg), or the combination of FF/VI was administered. The primary outcome was all-cause mortality. Exacerbations of COPD were an additional predefined endpoint. A total of 1,368 centers in 43 countries and 16,485 patients with moderate COPD and heightened cardiovascular risk were included in the study. MEASUREMENTS AND MAIN RESULTS: Compared with placebo, FF/VI reduced the rate of moderate and/or severe exacerbations by 29% (95% confidence interval [CI], 22-35; P < 0.001) and the rate of hospitalized exacerbations by 27% (95% CI, 13-39; P < 0.001). These relative effects were similar regardless of whether subjects had a history of exacerbation in the year before the study or an FEV1 <60% or ≥60% of predicted. The number needed to treat was not influenced by baseline FEV1 but was influenced by the history of exacerbations. FF/VI also reduced the rate of exacerbations treated with corticosteroids alone or with corticosteroids and antibiotics but not the rates of those treated with antibiotics alone. CONCLUSIONS:Patients with moderate chronic airflow obstruction experienced a reduction in exacerbations with FF/VI compared with placebo, irrespective of a history of exacerbations or baseline FEV1. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676; GSK Study number 113782).
Authors: William Z Zhang; Kazunori Gomi; Seyed Babak Mahjour; Fernando J Martinez; Renat Shaykhiev Journal: Am J Respir Crit Care Med Date: 2018-06-15 Impact factor: 21.405
Authors: Daniel Dedman; Sonia J Coton; Rebecca E Ghosh; Wilhelmine Meeraus; Courtney Crim; Catherine Harvey; Justyna Amelio; Sarah H Landis Journal: Pulm Ther Date: 2019-04-24
Authors: Diego J Maselli; Megan Hardin; Stephanie A Christenson; Nicola A Hanania; Craig P Hersh; Sandra G Adams; Antonio Anzueto; Jay I Peters; MeiLan K Han; Fernando J Martinez Journal: Chest Date: 2018-08-02 Impact factor: 10.262
Authors: Claus F Vogelmeier; Kenneth R Chapman; Marc Miravitlles; Nicolas Roche; Jørgen Vestbo; Chau Thach; Donald Banerji; Robert Fogel; Francesco Patalano; Petter Olsson; Konstantinos Kostikas; Jadwiga A Wedzicha Journal: Int J Chron Obstruct Pulmon Dis Date: 2018-04-10
Authors: Roberto W Dal Negro; Jadwiga A Wedzicha; Martin Iversen; Giovanni Fontana; Clive Page; Arrigo F Cicero; Edoardo Pozzi; Peter M A Calverley Journal: Eur Respir J Date: 2017-10-12 Impact factor: 16.671