Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Dongjak-gu, Seoul, Republic of Korea.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Jongno-Gu, Seoul, Republic of Korea.
Respiration. 2021;100(7):631-643. doi: 10.1159/000515133. Epub 2021 May 10.
Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD).
Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia.
We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757).
Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0-0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0-0.97]}.
There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.
各种吸入性皮质类固醇（ICS）、长效抗胆碱能药物（LAMA）和长效β-激动剂（LABA）的组合已被用作稳定型慢性阻塞性肺疾病（COPD）的三联疗法。
我们的研究旨在回答不同组合在疗效（降低加重或死亡率）和安全性（增加心血管事件或肺炎）方面是否存在显著差异。
我们在 PubMed、EMBASE、Cochrane 图书馆和临床试验注册处检索了从成立到 2019 年 12 月 31 日比较 ICS/LAMA/LABA 与其他吸入性药物在稳定型 COPD 患者中至少 12 周的平行组随机对照试验（RCT）。我们使用具有异质方差结构的随机效应模型（PROSPERO、CRD42019126757）进行贝叶斯网络荟萃分析。
在 21 项 RCT 中确定了 9 种不同的 ICS/LAMA/LABA 组合，包含 29892 例中至重度 COPD 患者。我们没有发现任何有意义的证据表明 ICS/LAMA/LABA 组合在减少总加重或全因死亡率方面有更好的疗效。ICS/LAMA/LABA 组合在中度至重度加重、COPD 相关死亡率或心血管疾病相关死亡率方面也没有差异，主要不良心血管事件的风险也没有差异。与 FP/tiotropium/SAL 和 FP/umeclidinium/SAL 相比，FP/glycopyrrolate/SAL 降低肺炎风险的作用显著（FP/glycopyrrolate/SAL 的中位优势比[OR]（95%可信区间[CrI]）=0[0-0.72]；FP/umeclidinium/SAL 的中位 OR[95% CrI] = 0[0-0.97]）。
在中至重度 COPD 患者中，各种 ICS/LAMA/LABA 组合在临床结局方面，包括急性加重和全因死亡率，没有显著差异。
