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
Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Hospitals Trust, Manchester, United Kingdom.
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Massachusetts Chan, Worcester, Massachusetts.
Am J Respir Crit Care Med. 2025 Feb;211(2):205-214. doi: 10.1164/rccm.202312-2311OC.
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.
慢性阻塞性肺疾病（COPD）与心血管和心肺事件风险增加相关。在III期、为期52周的ETHOS试验（NCT02465567）中，与格隆溴铵/富马酸福莫特罗（GFF）或布地奈德/富马酸福莫特罗（BFF）双联疗法相比，布地奈德/格隆溴铵/富马酸福莫特罗（BGF）三联疗法降低了中度/重度急性加重率和全因死亡率。然而，BGF与GFF相比对心血管事件的影响尚未评估。此外，BGF对首次严重急性加重时间的影响也未报道。为了评估ETHOS试验中BGF 320/18/9.6μg（BGF 320）和其他含吸入性糖皮质激素的治疗组与GFF相比对COPD患者心血管和严重心肺终点的影响。中度至极重度COPD且有急性加重病史的患者被随机分为每日两次的BGF 320、BGF 160/18/9.6μg、BFF 320/9.6μg或GFF 18/9.6μg（GFF）。首次严重COPD急性加重时间是一个预先设定的终点；心血管和严重心肺终点包括首次主要不良心脏事件时间、首次特殊关注的心血管不良事件（AE）时间、首次心脏AE时间以及首次严重心肺事件复合终点时间。与GFF相比，BGF 320降低了心血管和严重心肺事件的首次发生率（风险比[95%置信区间]），包括首次特殊关注的心血管不良事件时间（0.63[0.48, 0.82]）、心脏AE（0.60[0.48, 0.76]）和严重心肺事件（0.80[0.67, 0.95]）。在中度至极重度COPD患者中，与GFF相比，BGF对心血管终点和严重心肺事件有益。
