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Fluoroquinolone and Aortic Aneurysm or Dissection
Quick Takes
- In a large, nationwide population-based, observational study, there was no significant difference in the risk of hospitalization or in-hospital death due to aortic aneurysm (AA) or aortic dissection (AD) between outpatients who received a prescription for a fluoroquinolone (FQ) and those who received a prescription for a third-generation cephalosporin (3GC).
- There was a nonsignificant trend toward increased risk ratio of AA/AD during an ‘at-risk’ interval (7-187 days after the prescription) compared to pre-risk or post-risk intervals for 3GC recipients but not FQ recipients.
Study Questions:
Is there an increased risk of aortic aneurysm (AA) or aortic dissection (AD) associated with fluoroquinolone (FQ) use?
Methods:
Health care reimbursement data from the universal single-payer National Health Insurance Service (NHIS) of the Republic of Korea was used in a nationwide population-based study to identify adults ≥20 years old who received a prescription for an oral FQ or a third-generation cephalosporin (3GC) during an outpatient visit from 2005 to 2016. Patients were excluded if there was a prior history of AA or AD, or if there was concurrent use of both medications. The primary outcome measure was hospitalization or in-hospital death with a primary diagnosis of AA/AD. A Cox proportional hazards model was used to compare between FQ and 3GC groups the risk for the primary outcome up to 1 year after the index date of antibiotic first prescription. A self-controlled case series analysis was used to compare within each group the incidence of the primary outcome during the at-risk time interval (7-187 days after the index date of antibiotic prescription), the pre-risk period (6-12 months before the index date), and the post-risk period (6-12 months after the index date).
Results:
A total of 954,308 patients (777,109 with FQ and 177,199 with 3GC use) were included. The incidence rate ratios for AA/AD between the risk period and the pre-risk period were higher in the 3GC group (11.00; 95% confidence interval [CI], 1.42–85.20) compared to the FQ group (2.00; 95% CI, 0.97–4.12). The overall incidence of AA/AD among patients who received FQ and 3GC was 5.40 and 8.47 per 100,000 person-years, respectively. There was no significant difference in the risk between the two groups (adjusted hazard ratio, 0.752; 95% CI, 0.515–1.100) in the inverse probability of treatment-weighted Cox proportional hazards model. Subgroup and sensitivity analysis showed consistent results.
Conclusions:
There was no significant difference in the risk of AA/AD among patients who were prescribed an oral FQ compared to those prescribed an oral 3GC. The authors conclude that the study findings suggest that FQ use should not be deterred when it is clinically indicated.
Perspective:
Some studies have suggested an association between FQ use and aortic adverse events, leading to a US Food and Drug Administration warning regarding increased risk of AD or aortic rupture. However, other studies have suggested that the indication for antibiotic use rather than the specific antibiotic was more closely associated with the occurrence of adverse vascular events, potentially related to the role of infection in systemic inflammation, direct invasion of the arterial wall, or hemodynamic instability.
This large, nationwide population-based, observational study using the Republic of Korea NHIS compared hospitalization or in-hospital death due to AA/AD both between FQ and 3GC antibiotic prescription recipients; and (within each group of antibiotic recipients) between an ‘at-risk’ interval (7-187 days after the prescription), a pre-risk interval (6-12 months before the prescription), and a post-risk interval (6-12 months after the prescription). The study found that: 1) there was no significant difference in the risk of AA/AD between the two antibiotic groups, and 2) there was a nonsignificant trend toward increased risk ratio of AA/AD during the ‘at-risk’ interval for 3GC recipients but not FQ recipients.
The study provides reassurance that FQ use might not be associated with aortic risk or that any risk might be small, but it is not able to address whether FQ exposure might have late adverse effects, whether FQ exposure over a longer time interval might have cumulative adverse effects, or whether FQ exposure has higher risks among patients with pre-existing aortic disease.
Clinical Topics: Cardiac Surgery, Vascular Medicine, Aortic Surgery, Novel Agents, Statins
Keywords: Aneurysm, Dissecting, Aortic Aneurysm, Cephalosporins, Fluoroquinolones, Vascular Diseases
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