Prevention of COPD with Tiotropium or Salmeterol

Patients with exacerbations of chronic obstructive pulmonary disease (COPD) may be experiencing instability or worsening of their disease. Worldwide, COPD is the leading cause of disability and death, and exacerbations have been associated with the development of complications, worsening for coexisting conditions, reduced lung function, reduced health status and physical activity, and an increased risk of death. A primary treatment goal for patients with COPD is prevention of exacerbations. Current guidelines for treatment for COPD recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations. However, the guidelines do not specify whether a long-acting anticholinergic drug or a beta2-agonist is the preferred drug. Researchers recently conducted a trial to determine whether tiotropium (an anticholinergic drug) is superior to salmeterol (a beta2-agonist) in preventing exacerbations of COPD. They reported trial results in the New England Journal of Medicine [2011;364(12):1093-1103]. In the 1-year, randomized, double-blind, double-dummy, parallel-group trial, 7376 patients were assigned to and treated with 18 mcg of tiotropium once daily (n=3707) or 50 mcg of salmeterol twice daily (n=3669). The main outcome measure was the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year. The 2 groups were balanced at baseline in characteristics, including coexisting conditions. The primary end point was the time to the first exacerbation of COPD. Secondary and safety end points included time-to-event end points, number-of-event end points, serious adverse events, and death. The researchers defined exacerbation as an increase in or new onset of >1 symptom of COPD (cough, sputum, wheezing, dyspnea, or chest tightness), with at least 1 symptom lasting ≥3 days and leading the patient’s attending physician to initiate treatment with systemic glucocorticoids, antibiotics, or both (moderate exacerbation) or to hospitalize the patient (severe exacerbation). In the tiotropium group, the time to first exacerbation was increased by 42 days compared with the salmeterol group (187 vs 145 days). The increase corresponded to a 17% reduction in risk with tiotropium (hazard ratio, 0.83; 95% confidence interval [CI], 0.77-0.90; P<.001). The risk of moderate exacerbations was reduced by 14% in the tiotropium group compared with the salmeterol group (hazard ratio, 0.86; 95% CI, 0.79-0.93; P<.001). The risk of severe exacerbations was reduced by 28% with tiotropium compared with salmeterol (hazard ratio, 0.72; 95% CI, 0.61-0.85; P<.001). With tiotropium, the annual rate of exacerbations was 0.64, compared with 0.72 in the salmeterol group, an 11% reduction in the rate of exacerbations (rate ratio, 0.89; 95% CI, 0.83-0.96; P=.002). The annual rate of moderate exacerbations was reduced by 7% with tiotropium compared with salmeterol (0.54 vs 0.59; rate ratio, 0.93; 95% CI, 0.86-1.00; P=.048); the annual rate of severe exacerbations was reduced by 27% with tiotropium compared with salmeterol (0.09 vs 0.13; rate ratio, 0.73; 95% CI, 0.66-0.82; P<.001). The incidence of serious adverse events, including adverse events leading to the discontinuation of treatment, was similar in both groups: in the tiotropium group, there were 64 deaths (1.7%) compared with 78 (2.1%) in the salmeterol group. In summary, the researchers stated, “tiotropium, as compared with salmeterol, significantly increased the time to the first moderate or severe exacerbation of COPD and significantly decreased the annual rate of exacerbations among patients with moderate-to-very-severe COPD. The benefit with tiotropium was seen consistently in all the major subgroups that were considered in this trial and was independent of the concomitant use of inhaled glucocorticoids.”