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Salmeterol and Asthma-Related Deaths

These results reinforce the view that long-acting ß-agonists should not be used as monotherapy.

Studies conducted since the 1960s have shown associations between overuse of inhaled ß-agonists and asthma deaths, and experts have debated whether these observations represent cause and effect. After the long-acting ß-agonist salmeterol (Serevent) was approved in the mid-1990s, the manufacturer was asked to conduct a large safety study. The results (first released 3 years ago) now have been published.

Researchers randomized 26,355 adolescents and adults with asthma (18% black) to receive either inhaled salmeterol or placebo twice daily, along with their usual asthma medications. Only 47% of subjects used inhaled corticosteroids at baseline. After 28 weeks, more salmeterol recipients than placebo recipients experienced the primary endpoint of respiratory death or requisite intubation (50 vs. 36 events); this difference did not quite reach statistical significance in the overall population, but it was significant among blacks (20 vs. 5 events). Several secondary endpoints were significantly more common in the salmeterol group than in the placebo group, including asthma-related deaths (13 vs. 3 deaths). Post hoc analyses of the effect of inhaled steroids on outcomes were inconclusive.

Comment: These findings led to the warning that now appears in the prescribing information for Serevent and Advair (the salmeterol-fluticasone combination). Because asthmatic patients in this study were rather poorly controlled, and many did not use inhaled corticosteroids, the relevance of the findings to current asthma practice is unclear. Nevertheless, editorialists note that these results reinforce the view that long-acting ß-agonists should not be used as monotherapy, but rather as add-on therapy when inhaled corticosteroids fail to control asthma optimally.

— Allan S. Brett, MD

Published in Journal Watch General Medicine February 17, 2006

Citation(s):

Nelson HS et al. The salmeterol multicenter asthma research trial: A comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006 Jan; 129:15-26.

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O'Byrne PM and Ädelroth E. ß₂ déjà vu. Chest 2006 Jan; 129:3-5.

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