Association Between Use of Fluoroquinolones and Risk of Mitral or Aortic Valve Regurgitation: A Nationwide Cohort Study

Abstract

Biological plausibility suggests that fluoroquinolones may lead to mitral valve regurgitation or aortic valve regurgitation (MR/AR) through a collagen degradation pathway. However, available real‐world studies were limited and yielded inconsistent findings. We estimated the risk of MR/AR associated with fluoroquinolones compared with other antibiotics with similar indications in a population‐based cohort study. We identified adult patients who initiated fluoroquinolones or comparison antibiotics from the nationwide Taiwanese claims database. Patients were followed for up to 60 days after cohort entry. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of MR/AR comparing fluoroquinolones to comparison antibiotics after 1:1 propensity score (PS) matching. All analyses were conducted by type of fluoroquinolone (fluoroquinolones as a class, respiratory fluoroquinolones, and non‐respiratory fluoroquinolones) and comparison antibiotic (amoxicillin/clavulanate or ampicillin/sulbactam, extended‐spectrum cephalosporins). Among 6,649,284 eligible patients, the crude incidence rates of MR/AR ranged from 1.44 to 4.99 per 1,000 person‐years across different types of fluoroquinolones and comparison antibiotics. However, fluoroquinolone use was not associated with an increased risk in each pairwise PS‐matched comparison. HRs were 1.00 (95% CI, 0.89–1.11) for fluoroquinolones as a class, 0.96 (95% CI, 0.83–1.12) for respiratory fluoroquinolones, and 0.87 (95% CI, 0.75–1.01) for non‐respiratory fluoroquinolones, compared with amoxicillin/clavulanate or ampicillin/sulbactam. Results were similar when fluoroquinolones were compared with extended‐spectrum cephalosporins (HRs of 0.96, 95% CI, 0.82–1.12, HR, 1.05, 95% CI, 0.86–1.28, and HR, 0.88, 95% CI, 0.75–1.03, respectively). This large‐scale cohort study did not find a higher risk of MR/AR with different types of fluoroquinolones in the adult population.

Use of fluoroquinolones and the risk of aortic and mitral regurgitation: A nationwide case-crossover study

“…A recent nationwide cohort study in Taiwan found no link between FQs and an increased risk of mitral or aortic regurgitation [ 12 ]. They employed an active comparative study design, comparing FQs with amoxicillin/clavulanate among different individuals.…”

“…Other commonly prescribed antibiotics were selected as the negative control exposures, including amoxicillin, trimethoprim and sulfamethoxazole (TMP/SMX), amoxicillin clavulanate (AMC) and ampicillin sulbactam (ASB), and the second-generation drug cephalosporin. These antibiotics were chosen because their indications are generally similar to those of fluoroquinolones, according to treatment guidelines in Taiwan and other regions of Asia [ 12 ]. The definition of exposure was defined as a prescription ≥3 days in the outpatient department.…”

“…However, in a recent nationwide nested case–control study, FQs were not significantly associated with increased rates of valvular regurgitation, and their results did not support a possible causal connection between FQs exposure and incident valvular regurgitation [ 11 ]. Additionally, a recent nationwide cohort study in Taiwan found no link between FQs and an increased risk of mitral or aortic regurgitation [ 12 ]. These conflicting results emphasize the need for further research to confirm or refute whether FQs increase the risk of aortic and mitral regurgitation.…”