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.

中文翻译：

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三联疗法对 COPD 患者心血管和严重心肺事件的影响：随机、双盲、3 期临床试验 (ETHOS) 的事后分析。


理由：慢性阻塞性肺疾病（COPD）与心血管和心肺事件的风险增加有关。在为期 52 周的 III 期 ETHOS 试验 (NCT02465567) 中，与格隆溴铵/富马酸福莫特罗 (GFF) 双重治疗或布地奈德/富马酸福莫特罗（BFF）。然而，与 GFF 相比，BGF 对心血管事件的影响仍未得到评估。此外，BGF 对首次严重恶化时间的影响尚未有报道。目的：评估 BGF 320/18/9.6 μg (BGF 320) 和其他含有 ICS 的药物与 GFF 相比，对 ETHOS 慢性阻塞性肺病患者的心血管和严重心肺终点的影响。方法：有中度至极重度 COPD 且有加重史的患者被随机分配至每日两次 BGF 320、BGF 160/18/9.6 µg、BFF 320/9.6 µg 或 GFF 18/9.6 µg (GFF)。首次严重 COPD 恶化的时间是预先指定的终点；事后心血管和严重心肺终点包括首次主要不良心脏事件 (MACE) 的时间、首次特别关注的心血管不良事件 (AE) 的时间 (CVAESI)、首次心脏 AE 的时间以及首次复合终点的时间严重心肺事件。测量和主要结果：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 CVAESI（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]）。 结论：对于中度至极重度 COPD 患者，BGF 与 GFF 相比，在心血管终点和严重心肺事件方面具有益处。