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

Study Questions:

What is the association of long-acting inhaled β-agonist and anticholinergic use with the risk of hospitalizations and emergency department visits for cardiovascular events?


The investigators conducted a nested case-control analysis of a retrospective cohort study. They compared the risk of events between patients newly prescribed inhaled long-acting β-agonists and anticholinergics, after matching and adjusting for prognostic factors. Health care databases from Ontario, the largest province of Canada, with a multicultural population of approximately 13 million, were used for the analysis. 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, were included. The exposure of interest was new use of an inhaled long-acting β-agonist or long-acting anticholinergic. The main outcome measures were an emergency department visit or a hospitalization for a cardiovascular event.


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% confidence interval [CI], 1.12-1.52; p < 0.001 and 1.14; 95% CI, 1.01-1.28; p = 0.03). The authors found no significant difference in events between the two medications (adjusted odds ratio of long-acting inhaled β-agonists compared with anticholinergics, 1.15; 95% CI, 0.95-1.38; p = 0.16).


The authors concluded that among older individuals with COPD, new use of long-acting β-agonists and anticholinergics is associated with similar increased risks of cardiovascular events.


This large, observational, population-based study comparing the cardiovascular risk associated with long-acting anticholinergic and long-acting β-agonist use in older individuals with COPD found increased risks of hospitalization and emergency department visits for cardiovascular disease in new users of both medications, but no evidence of differing risk between medications. This lack of a difference was independent of sex, pre-existing cardiovascular disease, and COPD severity. These results support the need for close monitoring of all patients with COPD who require long-acting bronchodilators regardless of drug class. Additional prospective studies are indicated to determine what actually constitutes appropriate monitoring for these patients.

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: Pulmonary Disease, Chronic Obstructive, Canada, Cardiovascular Diseases, Ontario, Cholinergic Antagonists, Emergency Service, Hospital, Hospitalization, Bronchodilator Agents

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