Effect of Triple Therapy on Cardiovascular and Severe Cardiopulmonary Events in Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis of a Randomized, Double-Blind, Phase 3 Clinical Trial (ETHOS)

Chronic obstructive pulmonary disease (COPD) is associated with an 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...

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Veröffentlicht in:American journal of respiratory and critical care medicine Jg. 211; H. 2; S. 205
Hauptverfasser: Singh, Dave, Martinez, Fernando J, Hurst, John R, Han, MeiLan K, Gale, Chris P, Fredriksson, Martin, Kisielewicz, Dobrawa, Mushunje, Alec, Movitz, Charlotta, Ojili, Nikki, Parikh, Himanshu, Arya, Niki, Bowen, Karin, Patel, Mehul
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.02.2025
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ISSN:1535-4970
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Abstract Chronic obstructive pulmonary disease (COPD) is associated with an 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 compared with dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Furthermore, the effect of BGF on time to first severe exacerbation has not been reported. To assess the effects of BGF 320/18/9.6 μg (BGF 320) and other inhaled corticosteroid-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from the ETHOS trial. 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 prespecified endpoint; cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event, time to first cardiovascular adverse event (AE) of special interest, time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for time to first cardiovascular adverse event of special interest (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate to very severe COPD.
AbstractList Chronic obstructive pulmonary disease (COPD) is associated with an 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 compared with dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Furthermore, the effect of BGF on time to first severe exacerbation has not been reported. To assess the effects of BGF 320/18/9.6 μg (BGF 320) and other inhaled corticosteroid-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from the ETHOS trial. 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 prespecified endpoint; cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event, time to first cardiovascular adverse event (AE) of special interest, time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for time to first cardiovascular adverse event of special interest (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate to very severe COPD.
Author Kisielewicz, Dobrawa
Mushunje, Alec
Arya, Niki
Martinez, Fernando J
Patel, Mehul
Fredriksson, Martin
Hurst, John R
Ojili, Nikki
Han, MeiLan K
Bowen, Karin
Gale, Chris P
Movitz, Charlotta
Parikh, Himanshu
Singh, Dave
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  surname: Hurst
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  givenname: MeiLan K
  orcidid: 0000-0002-9095-4419
  surname: Han
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  givenname: Charlotta
  surname: Movitz
  fullname: Movitz, Charlotta
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  givenname: Niki
  surname: Arya
  fullname: Arya, Niki
  organization: AstraZeneca, Durham, North Carolina
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  surname: Bowen
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  orcidid: 0000-0003-0435-858X
  surname: Patel
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  organization: AstraZeneca, Cambridge, United Kingdom
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Keywords mortality
budesonide/glycopyrrolate/formoterol fumarate
hospitalization
cardiovascular
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References 39255455 - Am J Respir Crit Care Med. 2025 Feb;211(2):142-143. doi: 10.1164/rccm.202407-1494ED.
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Snippet Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular and cardiopulmonary events. In the phase III, 52-week ETHOS...
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StartPage 205
SubjectTerms Administration, Inhalation
Aged
Bronchodilator Agents - administration & dosage
Bronchodilator Agents - therapeutic use
Budesonide - administration & dosage
Budesonide - therapeutic use
Cardiovascular Diseases - etiology
Cardiovascular Diseases - prevention & control
Double-Blind Method
Drug Therapy, Combination
Female
Formoterol Fumarate - administration & dosage
Formoterol Fumarate - therapeutic use
Glycopyrrolate - administration & dosage
Glycopyrrolate - therapeutic use
Humans
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive - complications
Pulmonary Disease, Chronic Obstructive - drug therapy
Severity of Illness Index
Treatment Outcome
Title Effect of Triple Therapy on Cardiovascular and Severe Cardiopulmonary Events in Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis of a Randomized, Double-Blind, Phase 3 Clinical Trial (ETHOS)
URI https://www.ncbi.nlm.nih.gov/pubmed/39213002
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