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), aneurysm-related surgery (aHR:2.32; 95%CI:1.75-3.08) 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.