Is there an association between fluoroquinolone use and the rate of aortic aneurysms in US adults?
This cohort study of 47 596 545 antibiotic prescription fills among US adults aged 18 to 64 years found an increased rate of aortic aneurysms within 90 days after fluoroquinolone use compared with alternative antibiotic use, and when stratified by age, an increased incidence of aneurysms was observed in adults 35 years or older. No differences were seen when stratifying by sex and common comorbidities (eg, hypertension and hyperlipidemia); rather, the association of fluoroquinolone use with the aneurysm rate was consistent, suggesting a risk of drug class among both healthy and unhealthy individuals.
The results of this study suggested that fluoroquinolones should be used with caution among individuals aged 35 years or older, regardless of sex or comorbidities.
Although fluoroquinolones are commonly prescribed antibiotics in the US, recent international studies have shown an increased risk of aortic aneurysm and dissection after fluoroquinolone use, leading to US Food and Drug Administration warnings limiting use for high-risk patients. It is unclear whether these data are true for the US population and who is truly high risk.
To assess aortic aneurysm and dissection risks in a heterogeneous US population after fluoroquinolone use.
Design, Setting, and Participants
Prescription fills for fluoroquinolones or a comparator antibiotic from 2005 to 2017 among commercially insured individuals aged 18 to 64 years were identified in this retrospective analysis of MarketScan health insurance claims. This cohort study included 27 827 254 US adults (47 596 545 antibiotic episodes), aged 18 to 64 years, with no known previous aortic aneurysm or dissection, no recent antibiotic exposure, and no recent hospitalization.
Outpatient fill of an oral fluoroquinolone or comparator antibiotic (amoxicillin-clavulanate, azithromycin, cephalexin, clindamycin, and sulfamethoxazole-trimethoprim).
Main Outcomes and Measures
The 90-day incidence of aortic aneurysm and dissection. Inverse probability of treatment weighting in Cox regression was used to estimate the association between fluoroquinolone fill and 90-day aneurysm incidence. Interaction terms were used to assess the association of known risk factors (ie, sex, age, and comorbidities) with aneurysm after fluoroquinolone use. Data analysis was performed March 2019 to May 2020.
Of 47 596 545 prescription fills, 9 053 961 (19%) were fluoroquinolones and 38 542 584 (81%) were comparator antibiotics. The median (interquartile range) age of adults with fluoroquinolone fills was 47 (36-57) years vs 43 (31-54) years with comparator antibiotic fills. Women comprised 61.3% of fluoroquinolone fills and 59.5% of comparator antibiotic fills. Before weighting, the 90-day incidence of newly diagnosed aneurysm was 7.5 cases per 10 000 fills (6752 of 9 053 961) after fluoroquinolones compared with 4.6 cases per 10 000 fills (17 627 of 38 542 584) after comparator antibiotics. After weighting for demographic characteristics and comorbidities, fluoroquinolone fills were associated with increased incidence of aneurysm formation (hazard ratio [HR], 1.20; 95% CI, 1.17-1.24). More specifically, compared with comparator antibiotics, fluoroquinolone fills were associated with increased 90-day incidence of abdominal aortic aneurysm (HR, 1.31; 95% CI, 1.25-1.37), iliac artery aneurysm (HR, 1.60; 95% CI, 1.33-1.91), and other abdominal aneurysm (HR, 1.58; 95% CI, 1.39-1.79), and adults were more likely to undergo aneurysm repair (HR, 1.88; 95% CI, 1.44-2.46). When stratified by age, all adults 35 years or older appeared at increased risk (18-34 years: HR, 0.99 [95% CI, 0.83-1.18]; 35-49 years: HR, 1.18 [95% CI, 1.09-1.28]; 50-64 years: HR, 1.24 [95% CI, 1.19-1.28]; P = .04).
Conclusions and Relevance
This study found that fluoroquinolones were associated with increased incidence of aortic aneurysm formation in US adults. This association was consistent across adults aged 35 years or older, sex, and comorbidities, suggesting fluoroquinolone use should be pursued with caution in all adults, not just in high-risk individuals.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: October 7, 2020.
Published Online: January 6, 2021. doi:10.1001/jamasurg.2020.6165
Corresponding Author: Melina R. Kibbe, MD, Department of Surgery, University of North Carolina at Chapel Hill, 101 Manning Dr, Burnett Womack Bldg, Ste 4041, Chapel Hill, NC 27599-7050 (email@example.com).
Author Contributions: Drs Strassle and Kibbe contributed equally and are considered co–senior authors. Dr Kibbe had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Newton, Strassle, Kibbe.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: Newton, Strassle, Kibbe.
Statistical analysis: Newton, Strassle.
Obtained funding: Kibbe.
Administrative, technical, or material support: Strassle, Kibbe.
Conflict of Interest Disclosures: None reported.
Funding/Support: Dr Newton was supported by award T32GM086330 from the National Institutes of Health National Institute of General Medical Sciences.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Kibbe is the editor of JAMA Surgery, but she was not involved in any of the decisions regarding review of the manuscript or its acceptance.
Meeting Presentation: An early truncated version of this work, which did not include the data in this article, was presented at the American College of Surgeons Clinical Congress; October 30, 2019; San Francisco, California.
Additional Contributions: Alan C. Kinlaw, PhD, Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, assisted in identifying and classifying antibiotic indications.
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