Shelley R. Salpeter, MD; Nicholas S. Buckley; Thomas M. Ormiston, MD; Edwin E. Salpeter, PhD
Long-acting Î²-agonists may increase the risk for fatal and nonfatal asthma exacerbations.
To assess the risk for severe, life-threatening, or fatal asthma exacerbations associated with long-acting Î²-agonists.
English- and nonâ€“English-language searches of MEDLINE, EMBASE, and Cochrane databases; the U.S. Food and Drug Administration Web site; and references of selected reviews through December 2005.
Randomized, placebo-controlled trials that lasted at least 3 months and evaluated long-acting Î²-agonist use in patients with asthma. All trials allowed the use of as-needed short-acting Î²-agonists.
Outcomes measured were Peto odds ratio (OR) and risk difference of severe exacerbations requiring hospitalization, life-threatening exacerbations requiring intubation and ventilation, and asthma-related deaths. The OR for asthma-related deaths was obtained from the Salmeterol Multi-center Asthma Research Trial (SMART).
Pooled results from 19 trials with 33Â 826 participants found that long-acting Î²-agonists increased exacerbations requiring hospitalization (OR, 2.6 [95% CI, 1.6 to 4.3]) and life-threatening exacerbations (OR, 1.8 [CI, 1.1 to 2.9]) compared with placebo. Hospitalizations were statistically significantly increased with salmeterol (OR, 1.7 [CI, 1.1 to 2.7]) and formoterol (OR, 3.2 [CI, 1.7 to 6.0]) and in children (OR, 3.9 [CI, 1.7 to 8.8]) and adults (OR, 2.0 [CI, 1.1 to 3.9]). The absolute increase in hospitalization was 0.7% (CI, 0.1% to 1.3%) over 6 months. The risk for asthma-related deaths was increased (OR, 3.5 [CI, 1.3 to 9.3]), with a pooled risk difference of 0.07% (CI, 0.01% to 0.1%).
The small number of deaths limited the reliability in assessing this risk, and 28 studies did not report information on the outcomes of interest.
Long-acting Î²-agonists have been shown to increase severe and life-threatening asthma exacerbations, as well as asthma-related deaths.
Long-acting β-agonists may help improve asthma symptoms, but they also may increase risks for adverse outcomes.
This meta-analysis summarizes data from 19 randomized, placebo-controlled trials involving 33 826 participants with asthma. Compared with placebo, long-acting β-agonists increased severe exacerbations requiring hospitalization (odds ratio, 2.6 [95% CI, 1.6 to 4.3]), life-threatening exacerbations (odds ratio, 1.8 [CI, 1.1 to 2.9]), and asthma-related deaths (odds ratio, 3.5 [CI, 1.3 to 9.3]; risk difference, 0.07%). Risks were similar for salmeterol and formoterol and in children and adults.
Several trials did not report information about potential harms, and the number of reported deaths was small.
SMART = Salmeterol Multi-center Asthma Research Trial.
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-Analysis: Effect of Long-Acting β-Agonists on Severe Asthma Exacerbations and Asthma-Related Deaths. Ann Intern Med. 2006;144:904-912. doi: 10.7326/0003-4819-144-12-200606200-00126
Download citation file:
Published: Ann Intern Med. 2006;144(12):904-912.
Asthma, Pulmonary/Critical Care.
Results provided by:
Copyright © 2017 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use
This PDF is available to Subscribers Only