Dual LABA/LAMA Therapy versus LABA or LAMA Monotherapy for COPD: A Systematic Review and Meta-analysis in Support of the American Thoracic Society Clinical Practice Guideline

Mammen MJ, Pai V, Aaron SD, Nici L, Alhazzani W, Alexander PE. Ann Am Thorac Soc. 2020; [published online ahead of print, 2020 Jun 12]. [CrossRef] [PubMed[

There is uncertainty on the optimal first-line therapy for symptomatic COPD. Long-acting beta-2-receptor agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) have long been mainstays of treatment, though it is still not clear if dual therapy with LABA/LAMA is superior to monotherapy for symptomatic COPD. The authors conducted a systematic review to answer the following question: In patients with COPD who complain of dyspnea and/or exercise intolerance, is LABA/LAMA combination therapy more effective and equally safe compared to LABA or LAMA monotherapy? 24 studies were eligible for inclusion (n=45,441). Pairwise random-effects meta-analysis revealed reductions in hospital admissions (11% reduction, p<0.01) and acute exacerbations of COPD (20% reduction, p<0.002), all in favor of LABA/LAMA dual therapy. Although there is reduced dyspnea (0.10 standardized mean difference (SMD), p<0.001) and improved health-related quality of life (-0.13 standardized mean difference (SMD), p<0.001), both values did not meet a clinical meaningful difference threshold. LABA/LAMA combination therapy showed no difference in treatment-emergent adverse effects (risk ratio=0.99, p=0.34) when compared to either LAMA or LABA monotherapy. The authors conclude that based on the reviewed evidence, dual LABA/LAMA therapy is superior to either LABA or LAMA monotherapy based on the reduced risk of exacerbations and hospitalizations in patients with symptomatic COPD.