Formoterol mono- and combination therapy with tiotropium in patients with COPD: A 6-month study

Although guidelines recommend combining long-acting bronchodilators in COPD, data are limited. We examined the clinical efficacy and safety of formoterol, tiotropium and the combination in patients with COPD. Eight hundred and forty-seven patients with COPD (mean FEV1 52% predicted; FEV1/FVC 53%) were randomized to receive one of the following four treatments for 24 weeks: formoterol 10 μg b.i.d. plus tiotropium 18 μg o.d.; formoterol 10 μg b.i.d.; tiotropium 18 μg o.d., or placebo. The study was partially blinded (formoterol and placebo). For the primary endpoint, FEV1 2 h post-dose after 24 weeks, there were small differences in favour of the combination therapy versus formoterol (0.07 L, p = 0.044) or tiotropium (0.06 L, p = 0.066). All three treatments were superior to placebo (p < 0.001). The combination was statistically superior to monotherapy for: the primary endpoint (p = 0.044 vs. formoterol); FEV1 5 min after the first dose (p < 0.001) and at 12 weeks (p < 0.05 vs. tiotropium); and peak expiratory flow averaged over the first 6 weeks (p < 0.001 vs. both). The three active treatments were significantly more effective than placebo for secondary endpoints: COPD-related 'bad days', symptoms, use of rescue medication and peak expiratory flow, and aspects of health-related quality of life. The overall incidence of adverse events was similar with all active treatments, although COPD-related adverse events were more common with tiotropium. Combined bronchodilator therapy may be a valuable treatment option for patients with COPD.