1. Am J Med. 2010 Apr;123(4):322-8.e2. doi: 10.1016/j.amjmed.2009.07.035. Epub 2010 
Feb 20.

Long-acting beta-agonists with and without inhaled corticosteroids and
catastrophic asthma events.

Salpeter SR(1), Wall AJ, Buckley NS.

Author information: 
(1)Stanford University School of Medicine, Stanford, CA, USA.

Comment in
    Ann Intern Med. 2010 Sep 21;153(6):JC3-5.
    Am J Med. 2011 Mar;124(3):e11; author reply e13.
    Am J Med. 2010 Oct;123(10):e15; author reply e17.

BACKGROUND: It is unclear whether long-acting beta-agonists with concomitant
inhaled corticosteroids increase asthma-related intubations and deaths. We pooled
data on long-acting beta-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 beta-agonists
compared with placebo or long-acting beta-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
beta-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 beta-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 beta-agonists increase the risk for asthma-related
intubations and deaths, even when used in a controlled fashion with concomitant
inhaled corticosteroids.

DOI: 10.1016/j.amjmed.2009.07.035 
PMID: 20176343  [Indexed for MEDLINE]