Fluoroquinolones Associated With Increased Aortic Aneurysm Risk

Treatment with fluoroquinolones was associated with a 20% higher incidence of newly diagnosed aortic aneurysm compared to treatment with other antibiotics, according to an analysis published in JAMA Surgery.

The US Food and Drug Administration (FDA) issued a warning for fluoroquinolones in 2018 based on international studies linking increased risk of aortic aneurysm and dissection after use. Fluoroquinolones remain the most commonly prescribed antibiotic in long-term care facilities in the United States.

Investigators conducted a retrospective observational analysis of outpatient prescription fills for fluoroquinolones or comparator antibiotics (amoxicillin-clavulanate, azithromycin, cephalexin, clindamycin, and sulfamethoxazole-trimethoprim) between January 1, 2005, and September 30, 2017, among patients aged 18 to 64 years with no recent history of aortic aneurysm or dissection, antibiotic exposure, or hospitalization.

The main study outcome was the 90-day incidence of aortic aneurysm and dissection per 10,000 antibiotic fills. Investigators also analyzed the association between aortic aneurysm and dissection development after antibiotic use and known aneurysm risk factors such as sex, age, and comorbidities including diabetes, hypertension, and hyperlipidemia.

Of 47,596,545 antibiotic prescriptions, 19% were fluoroquinolones and 81% were comparator antibiotics. The median age of patients receiving fluoroquinolone fills was 47 years (interquartile range [IQR], 36-57) and the median age of patients with comparator antibiotic fills was 43 years (IQR, 31-54). Women comprised 61.3% of fluroquinolone fills vs 59.5% of comparator antibiotic fills.

The 90-day incidence of newly diagnosed aortic aneurysm was 7.5 cases per 10,000 fills after fluoroquinolones vs 4.6 cases per 10,000 fills after comparator antibiotics. Fluoroquinolones were associated with a higher incidence of aortic aneurysm (hazard ratio [HR], 1.20; 95% CI, 1.17-1.24), specifically for abdominal aortic aneurysm (HR, 1.31; 95% CI, 1.25-1.37), iliac artery aneurysm (HR, 1.60; 95% CI, 1.33-1.91), and other abdominal aneurysm (HR, 1.58; 95% CI, 1.39-1.79). There was no association between fluoroquinolone use and aortic dissection or thoracic aortic aneurysm.

The only significant risk factor investigators uncovered was age. Adults 35 years or older were at increased aneurysm risk (18-34 years: HR, 0.99 [95% CI, 0.83-1.18]; 35-49 years: HR, 1.18 [95% CI, 1.09-1.28]; 50-64 years: HR, 1.24 [95% CI, 1.19-1.28]; P =.04). Sex and comorbidities exhibited minimal risk differences between hazard ratios and no significant P values.

Smoking, an important risk factor for aneurysm development, was not evaluated since it was not captured in claims data.

Though the FDA’s warning against fluoroquinolone use singles out patients who are at high risk for aneurysm development, study authors concluded that age was the only determinant in aneurysm risk. “We believe that the current US FDA black box warnings are warranted but may need to be expanded to include younger adults with other risk factors,” they wrote.

Reference

Newton ER, Akerman AW, Strassle PD, Kibbe MR. Association of fluoroquinolone use with short-term risk of development of aortic aneurysm. JAMA Surg. Published online January 6, 2021. doi:10.1001/jamasurg.2020.6165