Treatment Of Tiotropium Plus Formoterol In Stable Chronic Obstructive Pulmonary Disease:a Meta-analysis

Background:Current guidelines for the treatment of chronic obstructive pulmonary disease (COPD) recommend the use of long-acting bronchodilators in the maintenance management of COPD. Combining bronchodilators that work through different mechanisms is recommended in patients with continuous symptoms.But it is currently unclear whether the combination therapy of a long-acting β2-agonist (formoterol) and the antimuscarinic tiotropium bromide (tiotropium) have additive effects on improving the lung function without increasing more adverse events in patients with chronic obstructive pulmonary disease (COPD).Objective:This meta-analysis was performed to evaluate the differences in efficacy and adverse events associated with combination therapy compared with tiotropium or formoterol alone, in patients with stable COPD.Methods:A MEDLINE, EMBASE,VIP, CNKI, CMB and Cochrane Controlled Trials Register (CCRT) search was carried out. Randomized controlled trials of2or more weeks of treatment with tiotropium plus formoterol or arformoterol, compared with tiotropium alone, were reviewed. Studies were pooled to yield odds ratio (OR) or weighted mean differences (WMD), with95%confidence interval (CI).Results:Fourteen trials, involving1955randomized patients, met the inclusion criteria. Treatment with tiotropium plus formoterol significantly improved the FEV1(WMD0.06L,95%CI:0.03,0.09),FEV1%(WMD4.72,95%CI:2.29,7.51),and reduced COPD exacerbations (OR=0.52;95%CI,0.33,0.84).Compared with tiotropium or formoterol alone, the difference was not statistically significant for FEV1/FVC (WMD1.53,95%CI:-2.41,5.46), The mean change in transitional dyspnoea index (TDI) was markedly greater with tiotropium plus formoterol (WMD=1.50,95%CI:1.01-1.99) than with tiotropium alone. There tended to be fewer adverse events with tiotropium plus formoterol (OR=0.90;95%CI,0.73,1.12), compared with tiotropium alone, but the differences were not statistically significant.Conclusions:Tiotropium plus formoterol significantly improved lung function and the change of TDI, and reduced the COPD exacerbations compared with tiotropium or formoterol alone. There was a trend towards a reduction in adverse events, although the difference was not statistically significant. Long-term trials are necessary to evaluate the effects of tiotropium plus formoterol and to clarify the role of combination therapy, compared with tiotropium or formoterol alone.