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Sarika Ogale, PhD; Todd A. Lee, PharmD, PhD; Sean D. Sullivan, PhD
Author and Funding Information

From the Department of Pharmacy (Drs Ogale and Sullivan), University of Washington; the Center for Management of Complex Chronic Care (Dr Lee), Edward Hines Jr VA Hospital; and the Center for Pharmacoeconomic Research, Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL.

Correspondence to: Todd A. Lee, PharmD, PhD, Edward Hines Jr VA Hospital (151-H), 5000 S 5th Ave, Hines, IL 60141; e-mail: todd.lee@va.gov


Dr Ogale is currently at Genentech, Inc.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Ogale is an employee of Genentech, Inc. Drs Lee and Sullivan have received funding for their contribution to the Burden of Obstructive Lung Disease (BOLD) Initiative, which has been funded in part by unrestricted educational grants to the Operations Center (www.boldcopd.org) from ALTANA, Aventis, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck, Novartis, Pfizer, Schering-Plough, Sepracor, and the University of Kentucky. Drs Lee and Sullivan have received past research grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, and GlaxoSmithKline. Dr Lee has participated in past advisory boards for AstraZeneca and Novartis.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(1):235-236. doi:10.1378/chest.10-0403
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To the Editor:

As Dr Singh notes, short-acting β2-agonists (SABAs) have been associated with an increased risk of cardiovascular events (CVEs) in observational studies,1,2 as well as in a metaanalysis of clinical trials.3 He suggests the increased risk of CVEs associated with ipratropium bromide in our study could be attributed to SABAs because the two drugs are commonly used concomitantly. In our analysis,4 we adjusted for the standardized number of inhaled SABA canisters and any use of oral or nebulized β2-agonists and long-acting β2-agonists during the past year. After adjustment for SABA use, we observed an increased risk of CVEs (hazard ratio [HR] for four or fewer and more than four 30-day equivalents: 1.40 [95% CI, 1.30-1.51] and 1.23 [95% CI, 1.13-1.36], respectively) associated with ipratropium exposure within the past 6 months.4 To further address the issue raised by Dr Singh, we reanalyzed the dataset, excluding patients receiving ipratropium bromide and SABA concurrently. This analysis confirmed our prior conclusion that there is an increased risk of CVE with ipratropium exposure within the past 6 months (HR, 1.32; 95% CI, 1.07-1.64), independent of SABA use.

Au DH, Curtis JR, Every NR, McDonell MB, Fihn SD. Association between inhaled beta-agonists and the risk of unstable angina and myocardial infarction. Chest. 2002;1213:846-851. [CrossRef] [PubMed]
 
Lemaitre RN, Siscovick DS, Psaty BM, et al. Inhaled beta-2 adrenergic receptor agonists and primary cardiac arrest. Am J Med. 2002;1139:711-716. [CrossRef] [PubMed]
 
Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest. 2004;1256:2309-2321. [CrossRef] [PubMed]
 
Ogale SS, Lee TA, Au DH, Boudreau DM, Sullivan SD. Cardiovascular events associated with ipratropium bromide in COPD. Chest. 2010;1371:13-19. [CrossRef] [PubMed]
 

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References

Au DH, Curtis JR, Every NR, McDonell MB, Fihn SD. Association between inhaled beta-agonists and the risk of unstable angina and myocardial infarction. Chest. 2002;1213:846-851. [CrossRef] [PubMed]
 
Lemaitre RN, Siscovick DS, Psaty BM, et al. Inhaled beta-2 adrenergic receptor agonists and primary cardiac arrest. Am J Med. 2002;1139:711-716. [CrossRef] [PubMed]
 
Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest. 2004;1256:2309-2321. [CrossRef] [PubMed]
 
Ogale SS, Lee TA, Au DH, Boudreau DM, Sullivan SD. Cardiovascular events associated with ipratropium bromide in COPD. Chest. 2010;1371:13-19. [CrossRef] [PubMed]
 
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