Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: A Systematic Review and Meta-Analysis

OBJECTIVES: We performed a systematic review and meta-analysis to explore the risk of an aortic aneurysm or aortic dissection following fluoroquinolone administration. METHODS: PubMed, Cochrane library, ClinicalTrials.gov, Embase and Google Scholar were systematically reviewed for controlled studies including adult patients exposed to fluoroquinolones with a primary outcome of aortic aneurysm or aortic dissection. RESULTS: The meta-analysis was conducted by pooling the effect estimates of four controlled observational studies (one case-control, one case-crossover and two cohort studies). Fluoroquinolone administration more than doubled the risk to develop aortic aneurysm or aortic dissection within 60 days following fluoroquinolone exposure (adjusted Relative Risk [RR] (95% confidence interval [CI]) = 2.14 (1.93 - 2.36); I2 = 15.8%). The quality of the finding was rated as moderate. The risk increase for aortic aneurysm alone was found to be significant (adjusted RR (95% CI) = 2.23 (2.01 - 2.45); I2 = 0%) while the risk increase for aortic dissection alone was not found to be significant (adjusted RR = 1.88 (0.11 - 3.65); I2 = 74%). In subgroup analysis, the risk increase for aortic aneurysm or aortic dissection appeared to be higher in females compared to males (RR = 1.87 (1.24 - 2.51); I2 = 0% versus RR = 1.58 (1.25 - 1.92); I2 = 0%, respectively) and higher in older patients compared to younger patients (RR = 1.72 (1.37 - 2.07); I2 = 0% versus RR = 1.47 (0.91 - 2.04); I2 = 0%, respectively). Subgroup analysis of two studies which measured the duration-response analysis found that as the duration of fluoroquinolone therapy increased from 3 to 14 days to greater than 14 days, there was an increased risk of aortic aneurysm or dissection. CONCLUSION: The findings of this meta-analysis confirm the positive association between fluoroquinolones and the development of aortic aneurysm or dissection. The data tend to show that this association may be majorly driven by aortic aneurysm. Additionally, some risk factors appear to prevail including prolonged fluoroquinolone treatment and older age.