Quinolone warning over aortic aneurysm risk

Along with several other recent studies, a nationwide Swedish cohort study published in the BMJ has raised concerns of a link between use of quinolones and the risk of aortic aneurysm or dissection.

The MHRA has advised that quinolones should only be used after careful benefit-risk assessment and consideration of other therapeutic options in patients at risk of aortic aneurysm or dissection. All patients should be advised to seek immediate medical attention in the event of sudden severe abdominal, chest or back pain.

Nationwide study

Identified from national health registers, the Swedish cohort included a total of 360,088 quinolone treatment episodes from 2006 to 2013, which were matched with a control group comprising an equal number of amoxicillin treatment episodes. The risks of a first diagnosis of aortic aneurysm or dissection (admission to hospital/emergency department or death due to aortic aneurysm or dissection) were compared in the two groups.

Within the 60-day period from the start of treatment, use of quinolones was associated with a 66% increased rate of aortic aneurysm or dissection compared with amoxicillin use, corresponding to an estimated absolute difference of 82 cases (95% CI 15–181) per 1 million treatment episodes.

In a secondary analysis from day 61 to 120, the researchers did not find a significant relationship between quinolone use and the occurrence of aortic aneurysm or dissection (hazard ratio 0.67, 95% CI 0.40–1.11). Moreover, of total aortic aneurysm or dissection cases among quinolone-treated patients, 41% occurred within the first 10 days of treatment.

Widespread use

The study bolsters the findings of previous studies that have reported an increased risk of aortic aneurysm or dissection associated with quinolones. The authors acknowledge that the absolute risk increase was relatively small, but highlight that the study's findings 'should be interpreted in the context of the widespread use of fluoroquinolones'.

Quinolones have been known to have damaging effects on collagen and other structural components of the extracellular matrix by inducing matrix metalloproteinases, enzymes thought to be involved in the pathogenesis of aortic aneurysms.

The MHRA’s advice follows a recent recommendation from the European Medicines Agency that the use of quinolone antibiotics be restricted owing to disabling and potentially long-lasting adverse effects associated with their use.