Effect of tiotropium bromide on the cardiovascular response to exercise in COPD

Introduction: Exercise limitation and exertional dyspnea are important symptoms of chronic obstructive pulmonary disease (COPD), which may be partially relieved by tiotropium. Although the mechanism of relief is multifactorial, improved dynamic ventilatory mechanics appear to be important. It is not however known whether tiotropium may also act by improving cardiovascular function during exercise. Methods: We conducted a randomized, placebo-controlled crossover study in 18 COPD subjects with a FEV1 40 +/- 3% predicted (mean +/- SEM). Subjects inhaled either tiotropium 18 mu g or placebo once daily for 7-10 days then the other intervention for a further 7-10 days after a 35-day washout period. Subjects performed constant work rate cycle exercise at 75% of maximum after each treatment period. Heart rate, blood pressure, oxygen uptake, operating lung volumes and breathing pattern were measured. Results: Heart rate was 7 beats/min lower at rest and throughout exercise with tiotropium compared to placebo (p = 0.001). Oxygen uptake was unchanged throughout exercise. Oxygen pulse on exercise was greater by 7.4% (p < 0.01) and systolic blood pressure was lower by 7 mmHg (p = 0.03). The cardiac rate pressure product was reduced by 7.6% (p < 0.01) with tiotropium. Exercise endurance tended to be greater with tiotropium. Reduction in heart rate on exercise correlated with an increase in inspiratory reserve volume (r = -0.50, p = 0.04). Conclusion: Tiotropium may improve cardiac as well as pulmonary function during exercise in COPD. We suggest that this effect may be due, in part, to improved cardiopulmonary interaction as a result of mechanical unloading of the ventilatory muscles however further study is required. ClinicalTrials.gov Identifier: NCT00274027. (c) 2007 Elsevier Ltd. All rights reserved.