Introduction

Long-acting muscarinic antagonists (LAMAs), long-acting β₂-agonists (LABAs), inhaled corticosteroids (ICS), and their combinations, are recommended for the treatment of chronic obstructive pulmonary disease (COPD). This study aimed to determine whether the safety and efficacy of aclidinium bromide differs by baseline maintenance LABA and ICS therapies.

Methods

ASCENT-COPD was a phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium 400 μg or placebo twice daily, via a multidose dry-powder inhaler for up to 3 years. Outcomes included time to first major adverse cardiovascular events (MACE), all-cause mortality, change from baseline in trough forced expiratory volume in 1 s (FEV₁), and COPD assessment test (CAT) total score over 3 years, and annual moderate-to-severe COPD exacerbation rate in patients receiving aclidinium or placebo with maintenance LABA monotherapy, ICS monotherapy, LABA + ICS (fixed/free), or no maintenance therapy (neither LABA nor ICS) at baseline.

Results

A total of 3589 patients were included (LABA, n = 227; ICS, n = 290; LABA + ICS, n = 2058; no maintenance, n = 1130). Aclidinium did not increase the risk of MACE or all-cause mortality versus placebo, regardless of baseline maintenance treatment. Reductions in moderate-to-severe exacerbation rates were observed with aclidinium versus placebo in all subgroups [LABA 43% (P = 0.046); ICS 25% (P = 0.202); LABA + ICS 22% (P = 0.003); no maintenance 18% (P = 0.130)]. Aclidinium improved morning trough FEV₁ irrespective of baseline therapy and CAT total scores, except for LABA and ICS subgroups, versus placebo at several time points.

Conclusion

In patients with moderate-to-severe COPD and CV risk factors, the addition of aclidinium to maintenance therapy with LABA or LABA + ICS provided further benefit.

Trial Registration

ClinicalTrials.gov identifier NCT01966107.

中文翻译：

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根据基线治疗阿地溴铵的疗效：ASCENT-COPD 随机试验的事后分析

介绍

长效毒蕈碱拮抗剂 (LAMA)、长效 β ₂受体激动剂 (LABAs)、吸入性皮质类固醇 (ICS) 及其组合被推荐用于治疗慢性阻塞性肺病 (COPD)。本研究旨在确定阿地溴铵的安全性和有效性是否因基线维持 LABA 和 ICS 疗法而异。

方法

ASCENT-COPD 是一项 4 期、多中心、双盲、随机、安慰剂对照、平行组研究，对象为中度至极重度 COPD 和心血管风险增加的患者。患者以 1:1 的比例随机接受阿地溴铵 400 μg 或安慰剂，每天两次，通过多剂量干粉吸入器持续长达 3 年。结果包括至第一次主要心血管不良事件 (MACE) 的时间、全因死亡率、1 秒内用力呼气谷量与基线相比的变化 (FEV ₁ ) 和 3 年内 COPD 评估测试 (CAT) 总分，以及年度中等在基线时，接受阿地溴铵或安慰剂与维持 LABA 单一疗法、ICS 单一疗法、LABA + ICS（固定/免费）或无维持疗法（既不是 LABA 也不是 ICS）的患者的重度 COPD 恶化率。

结果

共纳入 3589 名患者（LABA，n  = 227；ICS，n  = 290；LABA + ICS，n  = 2058；无维持治疗，n  = 1130）。与安慰剂相比，阿地溴铵不会增加 MACE 或全因死亡率的风险，无论基线维持治疗如何。在所有亚组中观察到阿地溴铵与安慰剂相比中度至重度恶化率降低 [LABA 43% ( P  = 0.046)；ICS 25% ( P  = 0.202); LABA + ICS 22% ( P  = 0.003); 无需维护 18% ( P  = 0.130)]。阿地溴铵改善了晨槽 FEV ₁不考虑基线治疗和 CAT 总分，除了 LABA 和 ICS 亚组，在几个时间点与安慰剂相比。

结论

在具有中度至重度 COPD 和 CV 危险因素的患者中，将阿地溴铵添加到 LABA 或 LABA + ICS 的维持治疗中提供了进一步的益处。

试用注册

ClinicalTrials.gov 标识符 NCT01966107。