Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study

Abstract

ObjectiveTo investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection.DesignNationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection.SettingSweden, July 2006 to December 2013.Participants360 088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360 088).Main outcome measuresCox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment.ResultsWithin the 60 day risk period, the rate of aortic aneurysm or dissection was 1.2 cases per 1000 person years among fluoroquinolone users and 0.7 cases per 1000 person years among amoxicillin users. Fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection (hazard ratio 1.66 (95% confidence interval 1.12 to 2.46)), with an estimated absolute difference of 82 (95% confidence interval 15 to 181) cases of aortic aneurysm or dissection by 60 days per 1 million treatment episodes. In a secondary analysis, the hazard ratio for the association with fluoroquinolone use was 1.90 (1.22 to 2.96) for aortic aneurysm and 0.93 (0.38 to 2.29) for aortic dissection.ConclusionsIn a propensity score matched cohort, fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection. This association appeared to be largely driven by aortic aneurysm.

Association of aortic aneurysm with fluoroquinolones

“…In a secondary analysis, the hazard ratio for the association with fluoroquinolone use was 1.9 (95% CI 1.2 to 3.0) for aortic aneurysm and 0.9 (95% CI 0.4 to 2.3) for aortic dissection 1. Additionally, there was no increased risk of aortic aneurysm or dissection associated with fluoroquinolone exposure in the period of 61–120 days from start of treatment, and 41% of cases of aortic aneurysm in patients treated with fluoroquinolones occurred in the first 10 days from start of treatment.…”

“…A Swedish cohort study has investigated a possible link between oral fluoroquinolones and an increased risk of aortic aneurysm or dissection 1. Fluoroquinolone use is known to increase the risk of tendon disorders, including Achilles tendon rupture and tendinopathy, through degradation of collagen and other structural tissues.…”

“…The study used linked registry data on patient characteristics, filled prescriptions and cases of aortic aneurysm or dissection between July 2006 and December 2013 1. It matched more than 360,000 treatment episodes using fluoroquinolones (78% ciprofloxacin, 20% norfloxacin) with comparator episodes using amoxicillin to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection (defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment).…”

“…Within the 60-day risk period, there were 64 cases of aortic aneurysm or dissection with fluoroquinolone use and 40 cases with amoxicillin use 1. This equated to a rate of 1.2 cases per 1,000 person-years among fluoroquinolone users and 0.7 cases per 1,000 person-years in amoxicillin users.…”

Fluoroquinolones and the aorta

“…In a linked article (doi:10.1136/bmj.k499), Pasternak and colleagues report a population based study of the association between outpatient treatment with fluoroquinolones (principally ciprofloxacin and norfloxacin) and aortic aneurysms and dissection 1. Compared with patients prescribed amoxicillin, those prescribed fluoroquinolones had a 66% increase in the 60 day risk of aortic aneurysm or dissection (hazard ratio 1.66, 95% confidence interval 1.12 to 2.46).…”