Combination therapy with tiotropium and salmeterol led to greater improvement in lung function parameters in patients with chronic obstructive pulmonary disease (COPD) than did the combination of fluticasone and salmeterol, reported Helgo Magnussen, MD, PhD, Hospital Grosshansdorf, Grosshansdorf, Germany.

Thoracic gas volume (TGV) improved significantly after 8 weeks of therapy with tiotropium+salmeterol (p<0.05), and exercise endurance time (EET) also improved.

The findings come from a randomized, crossover clinical trial to provide information about the relative effects of different combination maintenance therapies for COPD. Current clinical guidelines recommend combination therapy when response to single-agent therapy is suboptimal.

The study involved 309 patients whose mean age was 61 years and who had a mean baseline postbronchodilator forced expiratory volume at one second (FEV₁) of 1.36 L (47% of predicted), TGV of 5.42 L (165% of predicted), and EET of 458 seconds. The trial lasted 16 weeks, during which time patients were randomized to 8 weeks of therapy with tiotropium+salmeterol or fluticasone+ salmeterol and then crossed over to the opposite therapy for an additional 8 weeks of treatment.

The co-primary endpoints were TGV and EET at 8 weeks. The tiotropium+salmeterol combination led to significantly greater improvement in TGV compared with fluticasone+salmeterol, averaging 87 mL after 8 weeks (p=0.0482). The difference between groups emerged early and averaged 182 mL after 4 weeks (p<0.0001).

Improvement in EET did not differ significantly between groups, averaging 15 seconds more with tiotropium+salmeterol after 8 weeks. The difference averaged 26 seconds for patients who reported dyspnea and 12.5 seconds for patients who reported dyspnea and leg discomfort.

Several other parameters of lung function improved significantly during treatment with tiotropium+salmeterol. Postbronchodilator differences at 8 weeks were:

• FEV₁, 71 mL; p<0.0001

• Forced vital capacity, 154 mL; p<0.0001

• Inspiratory capacity, 115 mL; p=0.0005

• Residual volume, −154 mL; p=0.0011

The change from baseline in the Borg dyspnea score at exercise isotime favored tiotropium+salmeterol (−0.21; p=0.07) and was significantly greater after 4 weeks (−0.23; p<0.05).

The results demonstrated a significant shift in the locus of exercise-limiting symptoms from breathing discomfort (−20 patients) to leg discomfort (+35 patients) after treatment with tiotropium+salmeterol compared with fluticasone+salmeterol (−1, +19 patients; p=0.0056 between groups; Figure 1).

“This observation indicates that a ceiling effect on exercise duration may occur on leg deconditioning that can impact the potential improvements observed through improved lung mechanics,” Dr. Magnussen noted.