Lopez-Campos Jose Luis, Calero-Acuña Carmen, Márquez-Martín Eduardo, Quintana Gallego Esther, Carrasco-Hernández Laura, Abad Arranz Maria, Ortega Ruiz Francisco
Virgen del Rocio University Hospital, Biomedicine Institute of Seville (IBiS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Int J Chron Obstruct Pulmon Dis. 2017 Jun 23;12:1867-1876. doi: 10.2147/COPD.S132962. eCollection 2017.
The combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β-agonist (LABA) in a single inhaler is a viable treatment option for patients with chronic obstructive pulmonary disease (COPD). Here, we systematically review the current knowledge on double bronchodilation for the treatment of COPD, with a specific focus on its efficacy versus placebo and/or monotherapy bronchodilation.
A systematic review of clinical trials investigating LABA/LAMA combination therapies was conducted. Articles were retrieved from PubMed, Embase, and Scopus on June 26, 2016. We specifically selected clinical trials with a randomized controlled or crossover design published in any scientific journal showing the following characteristics: 1) comparison of different LABA/LAMA combinations in a single inhaler for patients with COPD, 2) dose approved in Europe, and 3) focus on efficacy (versus placebo and/or bronchodilator monotherapy) in terms of lung function, respiratory symptoms, or exacerbations.
We analyzed 26 clinical trials conducted on 24,338 patients. All LABA/LAMA combinations were consistently able to improve lung function compared with both placebo and bronchodilator monotherapy. Improvements in symptoms were also consistent versus placebo, showing some lack of correlation for some clinical end points and combinations versus monotherapy bronchodilation. Albeit being an exploratory end point, exacerbations showed an improvement with LABA/LAMA combinations over placebo in some trials; however, scarce information was available in comparison with bronchodilator monotherapy in most studies.
Our data show consistent improvements for LABA/LAMA combinations, albeit with some variability (depending on the clinical end point, the specific combination, and the comparison group). Clinicians should be aware that these are average differences. All treatments should be tailored at the individual level to optimize clinical outcomes.
长效毒蕈碱拮抗剂（LAMA）与长效β受体激动剂（LABA）联合于单一吸入器中，是慢性阻塞性肺疾病（COPD）患者的一种可行治疗选择。在此，我们系统回顾目前关于双重支气管扩张用于治疗COPD的知识，特别关注其与安慰剂和/或单一疗法支气管扩张相比的疗效。
对研究LABA/LAMA联合疗法的临床试验进行系统回顾。于2016年6月26日从PubMed、Embase和Scopus检索文章。我们特意选择发表在任何科学期刊上、具有随机对照或交叉设计的临床试验，其具有以下特征：1）针对COPD患者比较单一吸入器中不同LABA/LAMA组合；2）在欧洲获批的剂量；3）在肺功能、呼吸道症状或急性加重方面关注疗效（与安慰剂和/或支气管扩张剂单一疗法相比）。
我们分析了针对24338例患者开展的26项临床试验。与安慰剂和支气管扩张剂单一疗法相比，所有LABA/LAMA组合均始终能够改善肺功能。与安慰剂相比，症状改善也具有一致性，不过对于某些临床终点以及某些组合与单一疗法支气管扩张相比，显示出一定程度的缺乏相关性。尽管急性加重是一个探索性终点，但在一些试验中，LABA/LAMA组合与安慰剂相比急性加重有所改善；然而，在大多数研究中，与支气管扩张剂单一疗法相比，可用信息较少。
我们的数据显示LABA/LAMA组合具有持续改善效果，尽管存在一定变异性（取决于临床终点、具体组合和比较组）。临床医生应意识到这些是平均差异。所有治疗都应根据个体情况进行调整，以优化临床结局。
