Tiotropium plus formoterol versus tiotropium alone for stable moderate-to-severe chronic obstructive pulmonary disease: A meta-analysis.

PURPOSE: This meta-analysis was performed to compare the risks and benefits of combined treatment with tiotropium plus formoterol versus tiotropium alone for stable moderate-to-severe COPD. METHODS: A comprehensive search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) that compared formoterol plus tiotropium to tiotropium alone in COPD patients with a duration of at least 4 weeks. The cut-off date for the search was July 1, 2015. The odds ratio (OR) or mean difference (MD) was used to pool the results with 95% confidence intervals (CI). RESULTS: Eight randomized controlled trials were eligible for this meta-analysis. A significant improvement was observed among patients treated with tiotropium plus formoterol compared with tiotropium alone in the following spirometric indices: mean change in trough FEV1 (P = .02), trough FVC (P = .007), peak FEV1 (P < .00001), and peak FVC (P < .00001). A similar result was noted for the transitional dyspnea index (TDI) (MD 1.46; 95% CI 1.07-1.85) and a clinically significant change in TDI between the tiotropium plus formoterol and tiotropium alone groups (P < .00001). Moreover, a trend toward fewer adverse events was seen in the combination treatment group compared with the tiotropium group (OR .88; 95% CI .70-1.11), although this difference was not statistically significant. CONCLUSIONS: Compared with tiotropium alone, tiotropium in combination with formoterol improved lung function and the symptoms of dyspnea in stable moderate-to-severe COPD patients. Moreover, the combined treatment group tended to have fewer adverse events compared with the tiotropium treatment alone group.