| Autor: |
Singh D; Manchester University NHS Foundation Hospitals Trust, Medicines Evaluation Unit, University of Manchester, Manchester, United Kingdom of Great Britain and Northern Ireland., Martinez FJ; NewYork-Presbyterian Hospital, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, United States., Hurst JR; University College London, UCL Respiratory, London, United Kingdom of Great Britain and Northern Ireland., Han MK; University of Michigan, Division of Pulmonary and Critical Care, Ann Arbor, Michigan, United States., Gale CP; University of Leeds, Leeds Institute for Data Analytics, Leeds, United Kingdom of Great Britain and Northern Ireland.; University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, United Kingdom of Great Britain and Northern Ireland.; Leeds Teaching Hospitals NHS Trust, Department of Cardiology, Leeds, United Kingdom of Great Britain and Northern Ireland., Fredriksson M; AstraZeneca, Gothenburg, Sweden., Kisielewicz D; AstraZeneca, Barcelona, Spain., Mushunje A; AstraZeneca, Cambridge, United Kingdom of Great Britain and Northern Ireland., Movitz C; AstraZeneca, Gothenburg, Sweden., Ojili N; AstraZeneca, Gaithersburg, Maryland, United States., Parikh H; Formerly of AstraZeneca, Gaithersburg, Maryland, United States., Arya N; AstraZeneca, Durham, North Carolina, United States., Bowen K; AstraZeneca, Gaithersburg, Maryland, United States., Patel M; AstraZeneca, Cambridge, United Kingdom of Great Britain and Northern Ireland; mehul.patel1@astrazeneca.com. |
| Abstrakt: |
Rationale: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of cardiovascular and cardiopulmonary events. In the Phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality versus dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Further, the effect of BGF on time to first severe exacerbation has not been reported. Objective: Assess the effects of BGF 320/18/9.6 μg (BGF 320) and other ICS-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from ETHOS. Methods: Patients with moderate-to-very severe COPD and a history of exacerbations were randomized to twice-daily BGF 320, BGF 160/18/9.6 μg, BFF 320/9.6 μg, or GFF 18/9.6 µg (GFF). Time to first severe COPD exacerbation was a pre-specified endpoint; post-hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event (MACE), time to first cardiovascular adverse event (AE) of special interest (CVAESI), time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. Measurements and Main Results: BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for CVAESI (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). Conclusions: BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate-to-very severe COPD. |
