Calzetta Luigino, Rogliani Paola, Matera Maria Gabriella, Cazzola Mario
Department of Systems Medicine, Unit of Respiratory Clinical Pharmacology, University of Rome Tor Vergata, Rome, Italy.
Department of Systems Medicine, Unit of Respiratory Clinical Pharmacology, University of Rome Tor Vergata, Rome, Italy; Department of Systems Medicine, Chair of Respiratory Medicine, University of Rome Tor Vergata, Rome, Italy.
Chest. 2016 May;149(5):1181-96. doi: 10.1016/j.chest.2016.02.646. Epub 2016 Feb 26.
The wide availability of long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) fixed-dose combinations (FDCs) in the absence of head-to-head comparative pragmatic trials makes it difficult to choose which combination should be used. Therefore, we carried out a systematic review with meta-analysis that incorporated the data from trials lasting at least 3 months to evaluate the effectiveness of LAMA/LABA FDCs for COPD treatment.
Randomized controlled trials were identified by searching different databases of published and unpublished trials. We aimed to assess the influence of LAMA/LABA combinations on trough FEV1, transitional dyspnea index, St. George's Respiratory Questionnaire, and cardiac safety vs monocomponents.
Fourteen papers and one congress abstract with 23,168 patients with COPD (combinations, n = 10,328; monocomponents, n = 12,840) were included in this study. Our results showed that all LAMA/LABA combinations were always more effective than the LAMA or LABA alone in terms of the improvement in trough FEV1. Although there was not significant difference among LAMA/LABA combinations, we identified a gradient of effectiveness among the currently available LAMA/LABA FDCs. LAMA/LABA combinations also improved both transitional dyspnea index and St. George's Respiratory Questionnaire scores, but did not increase the cardiovascular risk when compared with monocomponents.
The gradient of effectiveness emerging from this meta-analysis is merely a weak indicator of possible differences between the various LAMA/LABA FDCs. Only direct comparisons will document if a specific LAMA/LABA FDC is better than the other. In the meanwhile, we believe it is only proper to consider that dual bronchodilation is better than a LAMA or a LABA alone, regardless of the drugs used.
在缺乏头对头比较性实用试验的情况下，长效毒蕈碱拮抗剂（LAMA）/长效β2受体激动剂（LABA）固定剂量组合（FDC）广泛可得，这使得难以选择应使用哪种组合。因此，我们进行了一项系统评价和荟萃分析，纳入了至少持续3个月的试验数据，以评估LAMA/LABA FDC治疗慢性阻塞性肺疾病（COPD）的有效性。
通过检索已发表和未发表试验的不同数据库来识别随机对照试验。我们旨在评估LAMA/LABA组合与单一成分相比，对最低FEV1、过渡性呼吸困难指数、圣乔治呼吸问卷以及心脏安全性的影响。
本研究纳入了14篇论文和1篇会议摘要，涉及23168例COPD患者（组合治疗组，n = 10328；单一成分治疗组，n = 12840）。我们的结果表明，就改善最低FEV1而言，所有LAMA/LABA组合始终比单独使用LAMA或LABA更有效。尽管LAMA/LABA组合之间没有显著差异，但我们在目前可用的LAMA/LABA FDC中确定了一个有效性梯度。LAMA/LABA组合还改善了过渡性呼吸困难指数和圣乔治呼吸问卷评分，但与单一成分相比，并未增加心血管风险。
该荟萃分析中出现的有效性梯度仅仅是各种LAMA/LABA FDC之间可能存在差异的一个微弱指标。只有直接比较才能证明特定的LAMA/LABA FDC是否优于其他产品。同时，我们认为无论使用何种药物，双重支气管扩张优于单独使用LAMA或LABA是合理的。
