Ann Am Thorac Soc. 2020 Jul 21. doi: 10.1513/AnnalsATS.202001-023OC. Online ahead of print.
OBJECTIVES: We conducted a systematic review and meta-analyses to estimate the safety and efficacy of using triple therapy (ICS/LABA/LAMA) compared to LABA/LAMA dual therapy or monotherapy with a single long-acting bronchodilator in patients with stable chronic obstructive pulmonary disease (COPD) who complain of dyspnea and/or exercise intolerance.
METHODS: A search of MEDLINE, EMBASE, and the Cochrane library databases was conducted for randomized controlled trials (RCTs) pertaining to the clinical question. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty/quality of the evidence.
RESULTS: Eleven studies were eligible for inclusion (n= 14,145 patients). Pairwise random-effects meta-analysis revealed an increase in the risk of pneumonia (relative risk = 1.47, 95% CI 1.20 to 1.80, p<0.001) and decreased risk of acute exacerbations of COPD (AECOPD) (relative risk = 0.75, 95% CI 0.68 to 0.82, p<0.001) with triple therapy compared to treatment with dual and monotherapy long-acting bronchodilator therapy. No significant difference in dyspnea scores (standardized mean difference = 0.09, 95% CI -0.02 to 0.19, p=0.09) or risk of hospitalization (rate ratio = 0.78, 95% CI: 0.58 - 1.06, p=0.11) was noted. When subgroup analysis was performed, based on inhaler class, no significant difference was noted between the groups in any of the critical outcomes studied. For patients with a history of one or more AECOPD in the past year, triple therapy resulted in 230 fewer AECOPD and 16 more pneumonias per 1,000 patients.
CONCLUSIONS: In patients with COPD who complain of dyspnea and/or exercise intolerance, triple therapy is not superior to maintenance long-acting bronchodilator therapy, except for patients with a history of one or more exacerbations in the past year, in whom the benefits of reduction in AECOPD outweigh the increased risk of pneumonia.