BACKGROUND AND PURPOSE:

• International studies have indicated that there may be a link between fluoroquinolone use and increased risk of aortic aneurysm and dissection
• FDA has issued a warning, but data is limited in the US, including a determination of which patients are at highest risk
• Newton et al. (JAMA Surg, 2021) assessed aortic aneurysm and dissection risks in a heterogeneous US population following fluoroquinolone use

METHODS:

• Retrospective cohort study
• Data source
  • MarketScan health insurance claims
• Participants
  • Commercially insured individuals
  • 18 to 64 years
  • Filled a prescription for fluoroquinolones or a comparator antibiotic from 2005 to 2017
  • Exclusion: Previous aortic aneurysm or dissection | Recent antibiotic exposure | Recent hospitalization
• Exposure
  • Outpatient fill of an oral fluoroquinolone
  • Comparator antibiotic | E.g., amoxicillin-clavulanate, azithromycin, cephalexin, clindamycin, and sulfamethoxazole-trimethoprim
• Study design
  • 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
• Primary outcomes
  • 90-day incidence of aortic aneurysm and dissection

RESULTS:

• 27,827,254 US adults | 47,596,545 antibiotic episodes
  • Fluoroquinolone fills: 19% | Comparator antibiotics: 81%
  • Median age of patient
    • Fluoroquinolone: 47 years; 61.3% women
    • Comparator antibiotics: 43 years; 59.5% women
• 90-day incidence of newly diagnosed aneurysm without taking in to account other risk factors
  • After fluoroquinolones: 7.5 cases per 10,000 fills
  • After comparators: 4.6 cases per 10,000 fills
• 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 to 1.24)
• Compared with comparator antibiotics, fluoroquinolone fills were associated with increased 90-day incidence of
  • Abdominal aortic aneurysm: HR 1.31 (95% CI, 1.25 to 1.37)
  • Iliac artery aneurysm: HR 1.60 (95% CI, 1.33, to 1.91)
  • Other abdominal aneurysm: HR 1.58 (95% CI, 1.39 to 1.79)
• Adults with fluoroquinolone fills were more likely to undergo aneurysm repair
  • HR 1.88 (95% CI, 1.44 to 2.46)
• When stratified by age, all adults 35 years or older appeared at increased risk (P = 0.04)
  • 18 to 34 years: HR 0.99 (95% CI, 0.83 to 1.18)
  • 35 to 49 years: HR 1.18 (95% CI, 1.09 to 1.28)
  • 50 to 64 years: HR 1.24 (95% CI ,1.19 to 1.28)
• Minor differences seen when above data stratified by
  • Sex | Diabetes | Hypertension | Hyperlipidemia

CONCLUSION:

• Fluoroquinolones were associated with an increase in aortic aneurysms in US adults
• This increased risk was found regardless of sex, comorbidities, and age suggesting that this drug class poses a risk in healthy and unhealthy individuals
• Limitations of this study included
  • Lack of confirmation whether medications were actually taken
  • Inability to identify patients who may have had an undiagnosed aneurysm prior to study inclusion (i.e., the drug aggravated a pre-existing condition)
• The authors state

Contextualizing these data, we believe that the current US FDA black box warnings are warranted but may need to be expanded to include younger adults with other risk factors

Learn More – Primary Sources:

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

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