Background 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. Methods Randomized controlled trials were identified by searching different databases of published and unpublished trials.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 FEV 1 , transitional dyspnea index, St. George's Respiratory Questionnaire, and cardiac safety vs monocomponents. Results 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 FEV 1 . 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. Conclusions 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.
