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Original Investigation
January 6, 2021

Association of Fluoroquinolone Use With Short-term Risk of Development of Aortic Aneurysm

Author Affiliations
  • 1Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill
  • 2Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill
  • 3Editor, JAMA Surgery
JAMA Surg. 2021;156(3):264-272. doi:10.1001/jamasurg.2020.6165
Key Points

Question  Is there an association between fluoroquinolone use and the rate of aortic aneurysms in US adults?

Findings  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.

Meaning  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.

Abstract

Importance  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.

Objective  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.

Exposures  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.

Results  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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