Abstract 4116300: Valvular Abnormalities and Risk of Abdominal Aortic Aneurysm Associated with Fluoroquinolone Use; A Retrospective Cohort Study

Introduction: Fluoroquinolones (FQ) are efficacious antibiotics whose antimicrobial effect is achieved through bacterial DNA gyrase inhibition. However, there is evidence suggesting that FQ may cause impaired collagen synthesis and an increase in tissue collagen degradation. Collagen serves as a predominant structural constituent of the aortic wall and heart valves. These structures undergo tissue maintenance, which necessitates the regulated expression of MMPs and TGF-β. In this study, we hypothesized that prolonged usage of FQs may increase risk of valvular abnormalities and abdominal aortic aneurysm. Methods: We conducted a retrospective cohort study utilizing de-identified patient data from the TriNetX platform, an extensive electronic health records (EHR) system. The cohorts consisted of smoker patients who used FQs for more than two consecutive weeks, Cohort A, N= 352,215 and smoker patients without a history of FQ use, Cohort B, N=350,912. Propensity score matching balanced baseline characteristics between cohorts: age, sex, ethnicity, and comorbidities. Results: The risk of developing AAA among smokers with a history of FQ use was 1.222% while the risk was 0.806% among smokers without history of FQ use (P< 0.0001, 95% CI (0.63,0.691), Risk Ratio (RR)= 0.66). The risk of developing nonrheumatic (NR) aortic insufficiency among smokers with history of FQ use was 1.479% while smokers with no history of fluoroquinolone use had a 0.95% risk (P<<0.0001, 95% CI (0.616,0.67), RR= 0.643). The risk of developing NR mitral insufficiency in smokers with history of FQ use was 3.873% versus their smoker FQ naive counterparts risk of 2.317% (P< 0.0001, 95% CI (0.582,0.615), RR= 0.598). NR tricuspid insufficiency in smokers with FQ usage was also increased versus their smoker FQ naive counterparts at 3.089% and 1.758%, respectively (P< 0.0001, 95% CI (0.552,0.587), RR =0.569). Conclusions: This study uncovered a significant association between FQ use, risk of AAA, and NR-valvular insufficiencies among smokers. In particular, male smokers are at highest risk of developing AAA. This same population is at risk for prostatitis that would likely need treatment with FQs, further increasing their risk. Despite the efficacy of this class of antibiotics, caution is paramount when prescribing FQs in individuals who are actively smoking or have any connective tissue pathologies.