Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD

Ziekenhuis Oost Limburg, Genck, Flemish, Belgium
European Respiratory Journal (Impact Factor: 7.64). 09/2005; 26(2):214-22. DOI: 10.1183/09031936.05.00140404
Source: PubMed


This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD). A total of 71 COPD patients (mean forced expiratory volume in one second (FEV1) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 microg q.d., formoterol 12 microg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV1, forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety. Compared with baseline (FEV1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV1 (0-12 h) than formoterol (127 versus 86 mL), while average night-time FEV1 (12-24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81, tiotropium 2.41 puffs x day(-1), formoterol 2.37 puffs x day(-1)). All treatments were well tolerated. In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.

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    • "Following proof of concept in terms of a benefit on FEV1 and in patients with acute exacerbations [70-72], several randomized controlled trials have reported improved lung function for tiotropium plus formoterol versus tiotropium alone [54-56,60,65,73]. Some trials have also identified significant improvements in symptom scores [55,56,60] and reductions in rescue medication use [47,49,55,56,65]. A recent meta-analysis confirmed the benefits of tiotropium plus formoterol on average FEV1, trough FEV1, and Transition Dyspnea Index (TDI) [74] (Table 3), with initial reports also suggesting that the combination may provide statistically significant improvements in effort-induced dynamic hyperinflation and exercise tolerance [75]. "
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