Fluoroquinolones Do Not Increase Hospitalization for Aortic Aneurysm or Dissection

Patients receiving fluoroquinolone are more likely to be hospitalized for aortic aneurysm or dissection compared with no fluoroquinolone use, but are not more likely to be hospitalized compared with other antibiotics, according to study results published in JAMA Cardiology.  

Researchers sought to assess the association between fluoroquinolone therapy, compared with other antibiotics, and hospitalization for aortic aneurysm or dissection. They pooled 2 separate UK patient primary care records—Aurum and GOLD—to separately conduct a cohort and case-crossover study in patients aged 18 years and older who were hospitalized and received treatment for an aortic aneurysm or dissection between April 1997 and December 2019.

In the cohort study, researchers pooled 1,077,584 patients prescribed fluoroquinolones (mean age, 52.7 years; women, 47.6%) and 2,056,537 patients prescribed cephalosporins (mean age, 52.2 years; women, 70.8%) from Aurum and 160,636 patients prescribed fluoroquinolones (mean age, 54.5 years; women, 49.5%) and 291,450 patients prescribed cephalosporins (mean age, 53.7 years; women, 71.0%) from GOLD.  The hazard ratio (HR) was estimated using the Cox regression model to assess the association between fluoroquinolone prescriptions and cephalosporin prescriptions relative to hospitalization with aortic aneurysm or dissection within 60 days of receiving the prescription. The researchers also adjusted for covariates such as demographics and lifestyle variables, prior comorbidities, risk factors for hospitalization with aortic aneurysm or dissection, and risk factors for tendon rupture. They used tendon rupture as a positive control outcome for patients that were prescribed fluoroquinolones.

In the case-crossover study, the researchers pooled 84,841 patients from Aurum and 10,357 patients from GOLD, who were hospitalized with aortic aneurysm or dissection. Patient characteristics such as age, sex, index date, and antibiotic use were matched 1:3 to control individuals. The odds ratio was used to estimate the association between fluoroquinolone use, the use of 3 comparator antibiotics (cephalosporin, co-amoxiclav [amoxicillin-clavulanate], and trimethoprim), and nonantibiotic use relative to the patient’s first hospitalization with aortic aneurysm or dissection.

Fluoroquinolone therapy significantly increased risk for aortic aneurysm or dissection hospitalization, compared with cephalosporin therapy (pooled HR, 1.28; 95% CI, 1.13-1.44; P <.001). After adjustment for covariates, the pooled adjusted HR (aHR) was 1.03 (95% CI, 0.91-1.17; P =.65), denoting an insignificant association. Patients who were prescribed fluoroquinolones also had a high risk for tendon rupture (pooled aHR, 1.98; 95% CI, 1.56-2.50; P <.001), confirming the primary control outcome. 

Compared with nonuse, fluoroquinolone therapy increased the odds of hospitalization with aortic aneurysm or dissection (pooled OR, 1.58; 95% CI, 1.37-1.83; P <.001). However, when compared to cephalosporin use (pooled OR, 1.05; 95% CI, 0.87-1.27; P =.59), trimethoprim use (pooled OR, 0.89; 95% CI, 0.75-1.06; P =.20), and co-amoxiclav use (pooled OR, 0.98; 95% CI, 0.82-1.18; P =.85); fluoroquinolones did not significantly increase the odds of hospitalization with aortic aneurysm or dissection.

A key study limitation is the potential for misclassification of antibiotic exposure, since medication adherence was not recorded. Ciprofloxacin accounted for the majority of fluoroquinolone prescriptions, which potentially limited the generalizability of findings to other antibiotics in the same drug class. Also, deaths from ruptured aneurysms and dissections before hospitalization were not identified.

“…infection itself may increase the risk of aortic aneurysm or dissection,” the researchers wrote. “Further research on the mechanism of increased risk could usefully inform patient care and infectious disease control and prevention.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.