Contrasting the Impact of Fluoroquinolone Exposure on Aortic Aneurysm and Dissection Risk: Insights from a US Multicenter Database Study

Aims To evaluate the association between fluoroquinolone (FQ) use and incident aortic aneurysm (AA), aortic dissection (AD), aneurysm-related surgery, and all-cause mortality in a large U.S. multicenter database and to explore the influence of comparator selection and infection-related confounding. Methods and Results A retrospective cohort of 180,936 patients prescribed FQs was compared with 180,936 propensity score–matched patients who received comparator antibiotics. Matching was conducted 1:1 based on demographics, socioeconomic status, lifestyle factors, comorbidities, and medication use. The primary outcome was the 90-day incidence of AA/AD, evaluated using adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). The FQ cohort was not found with an elevated risk of AA (aHR:0.95; 95%CI:0.83-1.08) but with elevated risk of AD (aHR:1.38; 95%CI:1.01-1.89) and mortality (aHR:2.75, 95%CI:2.62-2.89). Exploratory sensitivity analyses using alternative comparator groups yielded substantially different estimates, including lower observed risks of AA/AD when last-line antibiotics were used as comparators (AA: aHR, 0.53 [95%CI:0.47-0.60]; AD: aHR, 0.31 [95%CI:0.23-0.43]). These findings suggest important residual confounding related to comparator selection, infection indication, and infection severity. Conclusion In the primary analysis, FQ use was not associated with overall AA but was associated with increased risks of AD, aneurysm-related surgery, and mortality. Estimates varied substantially across comparator-based sensitivity analyses, suggesting potential residual confounding by indication and infection severity. These findings should not be interpreted as establishing the absence of AA/AD risk associated with FQ use.