Department of Cardiology, Qinghai Provincial People's Hospital, Xining, China.
Qinghai University Graduate School, Xining, China.
J Cardiovasc Pharmacol. 2019 Sep;74(3):255-265. doi: 10.1097/FJC.0000000000000705.
A majority of existing studies have focused on the efficacy of inhaled long-acting bronchodilators (ILABs), such as long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs), and LABAs combined with LAMAs in treating chronic obstructive pulmonary disease (COPD). The current meta-analysis aimed to investigate the correlation of ILABs with specific cardiovascular adverse events (CAEs). Five electronic databases, including PubMed, Embase, Cochrane Library, Scopus, and Web of Science were systematically retrieved. Finally, 16 randomized controlled trials were enrolled into the current meta-analysis. Typically, the efficacy of 3 major classes of drugs (LABAs, LAMAs, and LABAs combined with LAMAs), and 7 specific drugs (including formoterol, glycopyrrolate, indacaterol, olodaterol, Salmeterol, tiotropium, and vilanterol) for 4 CAEs, including myocardial infarction, cardiac failure (CF), ischemic heart disease (IHD), and stroke in stable COPD patients, was examined. All the pooled results were analyzed through the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). The direct meta-analysis results suggested that LABAs could increase the risk of CF in patients with stable COPD compared with placebo controls (OR 1.70, 95% CI, 1.00-2.90). In addition, network meta-analysis results indicated that LAMAs combined with LABAs would result in an increased risk of CF in patients with stable COPD (OR 2.31, 95% CI, 1.10-5.09). According to the ILABs specific drug analysis, formoterol may potentially have protective effects on IHD compared with placebo controls (OR 0.45, 95% CI, 0.18-1.00). In conclusion, among these 3 kinds of ILABs, including LAMAs, LABAs, and LABAs/LAMAs, for stable COPD patients, LAMAs and LABAs are associated with the least possibility to induce myocardial infarction and stroke, respectively. However, the application of LABAs will probably increase the risk of CF; they should be used with caution for stable COPD patients with CF. In addition, in specific-drug analysis, the use of formoterol can reduce the risk of treatment-related IHD. Nevertheless, more studies on different drug doses are needed in the future to further validate this conclusion.
大多数现有研究都集中在吸入长效支气管扩张剂（ILABs）的疗效上，例如长效抗毒蕈碱拮抗剂（LAMA）和长效β2-激动剂（LABA），以及 LABA 与 LAMA 的联合应用在治疗慢性阻塞性肺疾病（COPD）中的作用。本荟萃分析旨在研究 ILABs 与特定心血管不良事件（CAE）的相关性。系统检索了五个电子数据库，包括 PubMed、Embase、Cochrane 图书馆、Scopus 和 Web of Science。最终，有 16 项随机对照试验被纳入本荟萃分析。通常，三大类药物（LABA、LAMA 和 LABA/LAMA）和 7 种特定药物（包括福莫特罗、格隆溴铵、茚达特罗、奥洛达特罗、沙美特罗、噻托溴铵和维兰特罗）的疗效，用于治疗稳定型 COPD 患者的 4 种 CAE，包括心肌梗死、心力衰竭（CF）、缺血性心脏病（IHD）和中风，进行了评估。所有汇总结果均通过比值比（OR）及其相应的 95%置信区间（CI）进行分析。直接荟萃分析结果表明，与安慰剂对照组相比，LABA 可增加稳定型 COPD 患者 CF 的风险（OR 1.70，95%CI，1.00-2.90）。此外，网络荟萃分析结果表明，LAMA 与 LABA 联合应用会增加稳定型 COPD 患者 CF 的风险（OR 2.31，95%CI，1.10-5.09）。根据 ILABs 特定药物分析，与安慰剂对照组相比，福莫特罗可能对 IHD 有保护作用（OR 0.45，95%CI，0.18-1.00）。总之，在这 3 种 ILABs 中，包括 LAMA、LABA 和 LABA/LAMA，对于稳定型 COPD 患者，LAMA 和 LABA 分别与心肌梗死和中风的发生风险最低相关。然而，LABA 的应用可能会增加 CF 的风险；对于患有 CF 的稳定型 COPD 患者，应谨慎使用。此外，在特定药物分析中，使用福莫特罗可以降低治疗相关 IHD 的风险。然而，未来还需要更多关于不同药物剂量的研究来进一步验证这一结论。
