1. In this nested case-control study of Taiwanese patients, current and past use of fluoroquinolone antibiotics were associated with increased risk of aortic aneurysm and dissection.
Evidence Rating Level: 3 (Average)
Study Rundown: Fluoroquinolone use has been linked with increased risk of disorders of collagen degradation, including retinal detachment and Achilles tendinopathy. The aortic wall has a substantial structural component of collagen. This study of data from the Nation Health Insurance Research Database (NHIRD) of Taiwan examined the correlation between fluoroquinolone use and the risk of aortic dissection/aneurysm. Current, past, and any prior-year use were associated with increased risk of aortic dissection. There was a trend towards current fluoroquinolone use associated with increased risk of aortic disease requiring surgery, but this was not statistically significant. Increased duration of fluoroquinolone therapy trended towards increased risk of dissection or aneurysm, but this was also not statistically significant.
Strengths of the study include the relatively large sample size for rare events and dates on certain known confounders, which allowed for a robust propensity score analysis. The concordance between this study and previously published literature on fluoroquinolones and other collagen-based diseases also lends pathophysiologic consistency to the study. However, the investigation also has numerous limitations. It was a study of a Taiwanese population and may not be generalizable. The authors did not include data on lifestyle, such as smoking and obesity, making it difficult to account for these important cofactors. The study did not investigate the risk associated with other antibiotics or the underlying infections. There existed potential detection bias due to more aneurysms/dissections being diagnosed in patients getting radiologic investigations for potential infections requiring fluoroquinolone therapy.
Relevant Reading: Oral Fluoroquinolones and the Risk of Retinal Detachment
In-Depth [case-control]: This study utilized data from the NHIRD in Taiwan. Health records were obtained from 741,652 patients with age 18 years or older, from January 2000 to December 2011. The observation period was defined as from January 1, 2000 to end of study period, death, termination of health insurance, or diagnosis of aneurysm/dissection. The main outcome was aortic dissection or aneurysm, and was defined by criteria including diagnostic codes for aortic aneurysm and dissection with confirmation by radiographic evidence. The index date was the date of hospital admission or event date. Exposure was defined as a filled prescription for a fluoroquinolone containing medication with a prescription length of at least 3 days. Current, past, and prior uses were defined as within 60 days, 61 to 365 days prior, and within 365 days of the index date, respectively. For each case patient, 100 controls were selected.
Current fluoroquinolone use was linked to an increased rate ratio (RR) of aortic aneurysm or dissection (2.93 [2.17-3.97, 95% CI]). This association remained after adjusting for confounders (2.28 [1.67-3.13, 95% CI]) and propensity score (2.43 [1.83-3.22, 95% CI]). Past use of fluoroquinolones had a lower propensity score adjusted RR of 1.48 (1.18-1.86, 95% CI), while any fluoroquinolone use had a RR of 1.74 (1.44-2.09, 95% CI). Longer duration of therapy trended towards a larger propensity score adjusted rate ratio for aortic disease than shorter duration, though without statistical significance. Analysis of patients requiring surgery for dissection/aneurysm also demonstrated a non-significant trend towards increased risk associated with current fluoroquinolone use.
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