Oral Fluoroquinolone and the Risk of Aortic Dissection.

BACKGROUND: Previous studies raised safety concerns on the association between fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and dissection (AA/AD).

OBJECTIVES: This study sought to evaluate this association via a case-crossover analysis in a large national administrative database.

METHODS: A case-crossover design was used to compare the distributions of fluoroquinolone exposure for the same patient across a 60-day period before the AA/AD event (hazard period) and 1 randomly selected 60-day period (referent period) between 60 to 180 days before the AA/AD events. In the sensitivity analysis, the authors repeated the main analysis using a 1:5 ratio of hazard period to referent period, to adjust for the effect of time-variant confounders. A disease-risk score-matched time control analysis was performed to investigate the potential time-trend bias. The risks were calculated by a conditional logistic regression model.

RESULTS: A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95% CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure.

CONCLUSIONS: Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.