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Original Investigation |

Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals With Chronic Obstructive Pulmonary Disease

Andrea Gershon, MD, MS1,2,3,4; Ruth Croxford, MSc, PStat1; Andrew Calzavara, MSc1; Teresa To, PhD1,3,4; Matthew B. Stanbrook, MD, PhD4; Ross Upshur, MD, MSc1,2,4; Thérèse A. Stukel, PhD1,4
[+] Author Affiliations
1Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
2Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
3Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
4Department of Medicine, University of Toronto, Toronto, Ontario, Canada
JAMA Intern Med. 2013;173(13):1175-1185. doi:10.1001/jamainternmed.2013.1016.
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Importance  Chronic obstructive pulmonary disease (COPD) is a common and deadly disease. Long-acting inhaled β-agonists and anticholinergics, first-line medications for COPD, have been associated with increased risk of cardiovascular outcomes. When choosing between the medications, patients and physicians would benefit from knowing which has the least risk.

Objective  To assess the association of these classes of medications with the risk of hospitalizations and emergency department visits for cardiovascular events.

Design  We conducted a nested case-control analysis of a retrospective cohort study. We compared the risk of events between patients newly prescribed inhaled long-acting β-agonists and anticholinergics, after matching and adjusting for prognostic factors.

Setting  Health care databases from Ontario, the largest province of Canada, with a multicultural population of approximately 13 million.

Participants  All individuals 66 years or older meeting a validated case definition of COPD, based on health administrative data, and treated for COPD from September 1, 2003, through March 31, 2009.

Exposure  New use of an inhaled long-acting β-agonist or long-acting anticholinergic.

Main Outcome and Measures  An emergency department visit or a hospitalization for a cardiovascular event.

Results  Of 191 005 eligible patients, 53 532 (28.0%) had a hospitalization or an emergency department visit for a cardiovascular event. Newly prescribed long-acting inhaled β-agonists and anticholinergics were associated with a higher risk of an event compared with nonuse of those medications (respective adjusted odds ratios, 1.31 [95% CI, 1.12-1.52; P < .001] and 1.14 [1.01-1.28; P = .03]). We found no significant difference in events between the 2 medications (adjusted odds ratio of long-acting inhaled β-agonists compared with anticholinergics, 1.15 [95% CI, 0.95-1.38; P = .16]).

Conclusions and Relevance  Among older individuals with COPD, new use of long-acting β-agonists and anticholinergics is associated with similar increased risks of cardiovascular events. Close monitoring of COPD patients requiring long-acting bronchodilators is needed regardless of drug class.

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Figure.
Percentage of Individuals Experiencing Various Durations of Time From Receipt of an Inhaled Long-Acting β-Agonist (LABA) or Long-Acting Anticholinergic (LAA) to a Cardiovascular Event
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