Chest
Volume 121, Issue 3, March 2002, Pages 846-851
Journal home page for Chest

Clinical Investigations
Cardiology
Association Between Inhaled β-Agonists and the Risk of Unstable Angina and Myocardial Infarction

https://doi.org/10.1378/chest.121.3.846Get rights and content

Background

β-Adrenoceptor agonists (β-agonists) are commonly used to treat obstructive lung diseases, and preliminary studies have suggested they are associated with an increased risk of adverse cardiovascular outcomes. We further examined the association between acute coronary syndromes and inhaled β-agonist therapy.

Methods

We performed a nested, case-control study using data that were collected as part of a larger, ongoing, prospective study of quality improvement in the primary care clinics of seven Veterans Administration Medical Centers. We identified 630 patients with unstable angina or acute myocardial infarction hospitalized between 1996 and 1999. We frequency matched these case patients to 10,486 control subjects according to clinic location, and randomly assigned each an “index date.” The computerized pharmacy database at each center was used to ascertain β-agonist use. Cardiovascular risk factors were assessed from mailed questionnaires and electronic medical records, which included inpatient and outpatient diagnoses, medications, and laboratory results.

Results

In comparison with patients who had not filled a β-agonist prescription during the 90 days prior to their index date, patients who had filled a β-agonist prescription had an increased risk of experiencing an acute coronary syndrome. The increased risk of an acute coronary syndrome persisted after adjusting for age and cardiovascular risk factors, including hypertension, diabetes, and smoking history. Moreover, there was a dose-response relationship with an adjusted odds ratio (OR) of 1.38 for one to two metered-dose inhaler (MDI) canisters (95% confidence interval [CI], 0.86 to 2.23), an OR of 1.57 for three to five MDI canisters (95% CI, 1.01 to 2.46), and an OR of 1.93 for six or more MDI canisters (95% CI, 1.23 to 3.03). After stratifying for receipt of a β-blocker prescription, the adjusted OR in subjects who did not receive a β-blocker was 1.55 for one to two MDI canisters (95% CI, 0.60 to 3.99), an OR of 4.07 for three to five canisters (95% CI, 2.17 to 7.64), and an OR of 3.83 for six or more canisters (95% CI, 2.02 to 7.29). Subjects who had received both β-blockers and β-agonists had no increase in risk in acute coronary syndromes unless they had filled six or more β-agonist MDI canisters.

Conclusions

A prescription for inhaled β-agonists may increase the risk of myocardial infarction and unstable angina in patients with COPD.

Section snippets

Materials and Methods

The data for this study were collected as part of the Ambulatory Care Quality Improvement Project (ACQUIP). ACQUIP was a multicenter, randomized, clinical trial designed to test whether monitoring patients’ self-reported health and provision of regular reports to primary-care clinicians improves clinical outcomes and patients’ satisfaction. This study included those subjects who were enrolled in ACQUIP from December 1996 through May 1999. The study was clinic based and sought to enroll all

Results

We identified a total of 10,569 case patients and control subjects who had been sent a baseline health checklist questionnaire. Of these, 6,463 individuals (61%) had returned the health checklist questionnaire and had provided complete information. As expected, case patients and control subjects differed in a number of cardiovascular risk factors, including age, hypertension, number of pack-years smoked, and diabetes (Table 1). In addition, the prevalence of cardiovascular disease was

Discussion

We found that patients hospitalized for myocardial infarction or unstable angina were significantly more likely than control subjects to have received a β-agonist MDI during the 3 months immediately prior to their index date. We observed a dose-response relationship that did not appear to be confounded by tobacco use, COPD history, cardiovascular disease, or cardiovascular risk factors. Furthermore, the increased risk of an acute coronary syndrome was highest in those subjects who had not been

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Funding for this project was provided through the Department of Veterans Affairs and Health Services Research and Development, SDR96-002, Ambulatory Care Quality Improvement Project.

Dr. Au is supported by a Health Services Research and Development Fellowship from the Department of Veteran Affairs. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veteran Affairs.

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