Tiotropium more effective than salmeterol in preventing
exacerbations of COPD
A large, international, 1-year, randomized trial shows that the anticholinergic drug tiotropium is
more effective than the β2-agonist salmeterol in preventing exacerbations in patients with
moderate-to-very-severe COPD and a history of exacerbation.
Amy Dear, PhD
March 24, 2011 — In patients with moderate-to-very-severe chronic obstructive pulmonary
disease (COPD) and a history of exacerbations in the preceding year, tiotropium is superior to
salmeterol in preventing moderate and severe exacerbations, according to the findings of a new
Claus Vogelmeier, MD, from the Hospital of the Universities of Giessen and Marburg, in
Marburg, Germany and colleagues reported the findings in the March 24, 2011 issue of The New
England Journal of Medicine
According to background information in the article, long-acting bronchodilators benefit patients
with moderate-to-very-severe COPD. However, there is insufficient data comparing long-acting
anticholinergic agents such as tiotropium with long-acting β2-agonists such as salmeterol.
The Prevention of Exacerbations with Tiotropium in COPD (POET-COPD) trial studied 7376 patients with COPD. Inclusion criteria included a forced expiratory volume in 1 second (FEV1) after bronchodilation of ≤70% of the predicted value and a documented history of at least one exacerbation in the preceding year requiring therapy or hospitalization. Patients were randomly assigned to and treated with 18µg tiotropium once daily (3707 patients) or with 50µg salmeterol twice daily (3669 patients). Over the course of one year, clinic visits and monthly telephone calls were designed to collect details of the primary end point of time to the first moderate or severe exacerbation of COPD. Results showed that tiotropium prolonged the time to the first exacerbation by 42 days compared with salmeterol (187 days vs. 145 days), corresponding to a significant 17% reduction in risk of exacerbation (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P
<0.001). Specifically, tiotropium significantly reduced the risk of moderate exacerbations by 14% (hazard ratio, 0.86; 95% CI, 0.79 to 0.93; P
<0.001) and of severe exacerbations by 28% (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P
<0.001). In addition, tiotropium reduced the annual rate of exacerbations compared with the salmeterol group (0.64 vs. 0.72), corresponding to an 11% reduction in the rate of exacerbations (rate ratio, 0.89; 95% CI, 0.83 to 0.96; P
These effects were consistent across all patient subgroups and post hoc analyses showed that the reduction in risk of an exacerbation conferred by tiotropium was similar regardless of whether the patients received concomitant inhaled glucocorticoid therapy. The incidence of adverse events leading to the discontinuation of treatment and of serious adverse effects, including cardiovascular complications and death, was similar between the two groups. The authors conclude that “the results of this large trial provide data on which to base the choice of long-acting bronchodilator therapy for maintenance treatment of COPD.” According to independent commentator, William Bulman, MD, an assistant professor of Clinical Medicine with the Division of Pulmonary, Allergy and Critical Care Medicine at Columbia University College of Physicians and Surgeons, New York, “published guidelines for the management of COPD have gone a long way toward improving and standardizing care, but the recommendation for initiating long-acting bronchodilators in patients with moderate disease is nonspecific as to which particular medication to use. We now have evidence from a large, well-conducted study that indicates that tiotropium, an anticholinergic, may be a better choice than salmeterol, a β2-agonist, in selected patients.”
He added that “the goals of this study were focused and help clarify current guidelines, but the results should not be interpreted too broadly. The study does not address which medication might be best for patients with milder disease but who still meet criteria for a long-acting bronchodilator, and the study does not address which combination of medications might be best for patients with more severe disease.” In a related editorial, Jadwiga A. Wedzicha, MD,
with the Academic Unit of Respiratory Medicine, University College London Medical School, London, concurs that “the main implications of this trial are for the initial care of symptomatic patients with moderate disease and a history of recent exacerbations.” He adds that this trial “provides a good model for future COPD trials, which should be focused on a specific and relevant disease outcome” and suggests that “future trials involving patients with COPD will need to study which therapies and which specific combinations are optimal for which COPD phenotypes and disease severities, so that we can reduce the adverse effects of this disabling disease.” Five of the eight authors of the study and the editorialist report receiving consulting fees, grants, and other support from companies making bronchodilators. Boehringer Ingelheim formerly employed Dr. Hederer and currently employs Drs. Glaab and Schmidt. The study was funded by Boehringer Ingelheim and Pfizer. N Engl J Med. March 24, 2011;364:1093-1103, 1167-1168.
When Abortion Fails Occasionally abortion fails, especially when it is druginduced. When this happens, either a second D&C or a moreserious surgery may be attempted. The other alternative is adecision to continue the pregnancy and give birth to thebaby. In the case of “selective reduction” where only somefetuses are aborted from a multiple pregnancy (usually theresult of fertility treat
INVESTMENT AND FINANCIALSERVICES ASSOCIATION LIMITED Introduction IFSA is the national not-for-profit organisation representing thelife insurance industry to Government, regulatory agencies,This fact sheet explains how life insurance works in Australia andincludes information on the implications of being hepatitis Cpositive for future applications you may make for Life, Disabilityor Tra