A systematic review with meta-analysis of dual bronchodilation with LAMA/LABA for the treatment of stable COPD

BACKGROUND: The wide availability of long-acting muscarinic antagonist (LAMA)/longacting b2-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 METHODS: Randomized controlled trials were identified by searching different databases of published and unpublished trials.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 FEV1, 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 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. 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.