Fluoroquinolones Are Associated With Increased Risk of Aortic Aneurysm or Dissection: Systematic Review and Meta-analysis

Abstract

Fluoroquinolone use has been associated with collagen disease events, raising safety concerns. We hypothesized that the use of fluoroquinolones is associated with aortic aneurysm (AA) and aortic dissection or aortic rupture (AD/AR). We performed a systematic review with meta-analysis on studies published until March 2019. Seven observational studies were included, comprising 2,851,646 participants. The studies were evaluated regarding their risk of bias. Results on fluoroquinolone use risk comparing with nontreatment and with beta-lactam antibiotic use were extracted. The estimates were pooled through a random-effects model meta-analysis and heterogeneity assessed through the I² statistic. Sensitivity analysis were performed, grouping studies per design and with exclusion of studies with critical risk of bias. Fluoroquinolone use was associated with a higher risk of AA/AD/AR, comparing with a nontreatment intervention (odds ratio = 2.26; 95%CI 1.93-2.65; I² = 30%) and comparing with a beta-lactam intervention (odds ratio = 1.56; 95%CI 1.37-1.79; I² = 0%). This harm effect remained significant when pooling the results for the AD/AR outcome only and across various study designs. Studies comparing with beta-lactam intervention were considered to have a moderate risk of bias, while the remaining ones were classified as having at least a serious risk of bias. All evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation evidence. Fluoroquinolone use was associated with a significant risk of AA/AD/AR.

Keywords: Aortic aneurysm; Aortic dissection; Fluoroquinolone; Meta-analysis; Systematic review.