LAUSR

RATIONALE 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. OBJECTIVES To clarify the evidence landscape, we 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? METHODS A search of MEDLINE, EMBASE, and the Cochrane Library databases was conducted by a medical librarian for randomized controlled trials (RCTs) enrolling patients with COPD who complain of dyspnea and/or exercise intolerance, that compare LABA/LAMA combination therapy to LABA or LAMA monotherapy. A systematic approach was used to screen, abstract, and critically appraise the emerging study evidence. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty/quality of the evidence. RESULTS 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. CONCLUSIONS Based on the reviewed evidence, in patients with symptomatic COPD who complain of dyspnea and/or exercise intolerance, dual LABA/LAMA therapy is superior to either LABA or LAMA monotherapy based on the reduced risk of exacerbations and hospitalizations.