Long-acting Beta-Agonists with and without Inhaled Corticosteroids and Catastrophic Asthma Events
published online 22 February 2010.
Abstract
Background
It is unclear whether long-acting β-agonists with concomitant inhaled corticosteroids increase asthma-related intubations and deaths. We pooled data on long-acting β-agonists with variable and concomitant inhaled corticosteroids to evaluate the risk for catastrophic asthma events.
Methods
We conducted searches of electronic databases, the US Food and Drug Administration website, clinical-trials registries, and selected references through December 2008. We analyzed randomized controlled trials in patients with asthma, which lasted at least 3 months, evaluated long-acting β-agonists compared with placebo or long-acting β-agonists with inhaled corticosteroids compared with corticosteroids alone, and included at least 1 catastrophic event, defined as asthma-related intubation or death.
Results
In pooled trial data that included 36,588 participants, long-acting β-agonists increased catastrophic events 2-fold (Peto odds ratio [OR] 2.10; 95% confidence interval [CI], 1.37-3.22). Statistically significant increases were seen for long-acting β-agonists with variable corticosteroids compared with placebo (OR 1.83; 95% CI, 1.14-2.95) and for concomitant treatment with corticosteroids compared with corticosteroids alone (OR 3.65; 95% CI, 1.39-9.55). Similar increases in risk were seen for variable and concomitant corticosteroid use, salmeterol and formoterol, and children and adults. When the analysis was restricted to trials with controlled corticosteroid use, given as part of the study intervention, concomitant treatment still increased catastrophic events compared with corticosteroids alone (OR 8.19; 95% CI, 1.10-61.18).
Conclusion
Long-acting β-agonists increase the risk for asthma-related intubations and deaths, even when used in a controlled fashion with concomitant inhaled corticosteroids.
Reprint requests should be addressed to Shelley Salpeter, MD, 751 S. Bascom Ave, San Jose, CA 95128
Funding: Santa Clara Valley Medical Center, San Jose, Calif.
Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript. None of the authors have had any relationships with a pharmaceutical company that manufactures a β-agonist or other respiratory medications. Dr Salpeter has provided expert testimony on a litigation case involving a long-acting β-agonist and was paid on an hourly basis.
Authorship: All authors had access to the data and played a role in writing this manuscript.
ABSTRACT
