The anticholinergic drug tiotropium (brand name: Spiriva) is superior to the β2-agonist salmeterol (brand name: Serevent) as first-line maintenance therapy to prevent exacerbations of chronic obstructive pulmonary disease (COPD) in patients with moderate to very severe stages, a study found.
The Prevention of Exacerbations with Tiotropium in COPD (POET-COPD) trial was a one-year, randomized, double-blind, double-dummy, parallel-group trial at 725 centers in 25 countries. Researchers compared tiotropium to salmeterol to assess the incidence of moderate or severe exacerbations in patients with moderate to very severe COPD and a history of exacerbations in the previous year. A total of 7,376 patients were randomly assigned to and treated with 18 μg of tiotropium once daily or 50 μg of salmeterol twice daily between January 2008 and April 2009. The primary end point was the time to the first exacerbation, defined as an increase in or new onset of more than one symptom (such as cough, sputum, wheezing, dyspnea or chest tightness) with at least one symptom lasting three days or more and leading to treatment with systemic glucocorticoids, antibiotics, or both (moderate exacerbation) or to hospitalization (severe exacerbation). Results appeared in the March 24 New England Journal of Medicine.
Tiotropium increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio [HR], 0.83; 95% CI, 0.77 to 0.90; P<0.001). Because 36.5% (n=2,691) of patients had an exacerbation, time to the first exacerbation in the first quartile of patients was calculated instead of the median.
Tiotropium significantly reduced the annual rate of exacerbations by 11% (rate ratio, 0.89; 95% CI 0.83-0.96; P=0.002). It also reduced the risk of moderate exacerbations by 14% (HR, 0.86; 95% CI, 0.79 to 0.93; P<0.001) and of severe exacerbations by 28% (HR, 0.72; 95% CI, 0.61 to 0.85; P<0.001). In addition, tiotropium reduced the risk of exacerbations leading to treatment with systemic glucocorticoids by 23% (HR, 0.77; 95% CI, 0.69 to 0.85; P<0.001), treatment with antibiotics by 15% (HR, 0.85; 95% CI, 0.78 to 0.92; P<0.001), and treatment with both by 24% (HR, 0.76; 95% CI, 0.68 to 0.86; P<0.001). Benefits appeared as early as one month and lasted the duration of the one-year study. Serious adverse events, adverse events that stopped therapy, and deaths were similar between the two groups.
An editorialist wrote, “The main implications of this trial are for the initial care of symptomatic patients with moderate disease and a history of recent exacerbations. ... There is no evidence for the superiority of tiotropium in patients with mild COPD (those in whom the FEV1 is >70% of the predicted value) or symptomatic patients with moderate COPD but without a history of exacerbations.”
For more on managing COPD in hospitalized patients, read ACP Hospitalist's March cover story.