Kardos Peter, Worsley Sally, Singh Dave, Román-Rodríguez Miguel, Newby David E, Müllerová Hana
Group Practice and Respiratory, Allergy and Sleep Unit, Red Cross Maingau Hospital, Frankfurt, Germany.
GSK, Stockley Park, Middlesex.
Int J Chron Obstruct Pulmon Dis. 2016 Nov 25;11:2885-2895. doi: 10.2147/COPD.S118867. eCollection 2016.
Long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Although the efficacy of LAMAs and LABAs has been well established through randomized controlled trials (RCTs), questions remain regarding their cardiovascular (CV) safety. Furthermore, while the safety of LAMA and LABA monotherapy has been extensively studied, data are lacking for LAMA/LABA combination therapy, and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically designed to assess this. Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities. However, severe CV and other comorbidities are often exclusion criteria for RCTs, contributing to a lack in external validity and generalizability. Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs. We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies, and explore the advantages and limitations of data derived from each study type. We also describe an ongoing prospective, observational, comparative post-authorization safety study of a LAMA/LABA combination therapy (umeclidinium/vilanterol) and LAMA monotherapy (umeclidinium) versus tiotropium, with a focus on the relative merits of the study design.
长效毒蕈碱拮抗剂（LAMA）或长效β2受体激动剂（LABA）支气管扩张剂及其联合用药被推荐用于慢性阻塞性肺疾病（COPD）的维持治疗。尽管通过随机对照试验（RCT）已充分证实了LAMA和LABA的疗效，但关于它们的心血管（CV）安全性仍存在疑问。此外，虽然已对LAMA和LABA单药治疗的安全性进行了广泛研究，但缺乏LAMA/LABA联合治疗的数据，并且大多数报道LAMA/LABA联合治疗CV安全性的研究并非专门设计用于评估这一点。评估COPD治疗的CV安全性很重要，因为许多COPD患者存在潜在的CV合并症。然而，严重的CV和其他合并症通常是RCT的排除标准，这导致缺乏外部有效性和可推广性。真实世界观察性研究是评估COPD治疗在更广泛患者群体中的有效性和安全性的另一个重要工具，并且可以改善RCT的外部有效性局限性。我们研究了从RCT和真实世界观察性研究中已经了解到的关于LAMA/LABA联合治疗的CV和脑血管安全性的信息，并探讨了每种研究类型数据的优缺点。我们还描述了一项正在进行的关于LAMA/LABA联合治疗（乌美溴铵/维兰特罗）和LAMA单药治疗（乌美溴铵）与噻托溴铵对比的前瞻性、观察性、上市后安全性比较研究，重点关注研究设计的相对优点。
