麻豆传媒

For the first time, fluoroquinolone exposure was tied to aortic complications in patients with established aortic disease in a large study.

In the cohort study from Taiwan, people with an existing aortic dissection (AD) or aortic aneurysm (AA) were at higher risk of adverse outcomes during the periods they were exposed to fluoroquinolones:

• All-cause death: adjusted HR 1.61 (95% CI 1.50-1.73)
• Aortic death: adjusted HR 1.80 (95% CI 1.50-2.15)
• Aortic open surgery: adjusted HR 1.49 (95% CI 1.24-1.79)
• Aortic stent placement: adjusted HR 1.64 (95% CI 1.30-2.06)

By contrast, amoxicillin (Amoxil) exposure was not associated with any of these outcomes over follow-up averaging 3.5 years, according to Shao-Wei Chen, MD, PhD, of Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taiwan, and colleagues.

"Therefore, reducing FQ [fluoroquinolone] use in hospitalized patients with aortic disease is essential for patient safety. However, further large-scale studies or clinical trials should evaluate the safety of FQs, which are considered convenient and effective antibiotics, in the general population without any risk factors to avoid unnecessary panic," they stated in the .

Fluoroquinolone use had been blamed for new aortic disorders based on multiple large studies. Limitations of the observational analyses have led some to doubt if the connection is truly causal, however.

In any case, the other risks of these medications include mental health problems and potential low blood sugar adverse reactions. Previous work has also linked fluoroquinolones with adverse events such as hepatotoxic effects, torsade de pointes, and connective tissue disorders, Chen and colleagues noted.

Yet these antibiotics continue to be widely used: fluoroquinolones were prescribed for 23.6% of AA or AD patients over follow-up in the Taiwanese study.

This underscores how "future efforts to change prescribing practices will need to target both inpatient and outpatient settings. There will be a need for studies focused on designing strategies to implement evolving clinical practice recommendations and to evaluate and optimize their effectiveness," said Scott LeMaire, MD, of Baylor College of Medicine in Houston, in .

"In the meantime, given the life-threatening nature of the complications, it seems prudent to follow the existing FDA and European Medicines Agency warnings and avoid the use of these drugs in patients at risk for aortic complications, particularly those with existing aortic disease," according to the editorialist.

The retrospective cohort study relied on the Taiwan National Health Insurance Research Database. Included were 31,570 hospitalized adults (mean age 70.2; 72.6% men) who were subsequently discharged with a diagnosis of AD or AA from 2001 to 2013.

Authors performed a secondary active-comparator analysis that showed that the risks of all four outcomes were significantly higher in periods of fluoroquinolone rather than amoxicillin exposure.

Additionally, in a sensitivity analysis excluding the 5% of patients who had been prescribed fluoroquinolones in the 2 months prior to hospitalization, main results stayed robust, Chen and colleagues reported.

Besides the inherent limitations of observational studies, the present analysis had to rely on coding accuracy in the Taiwanese database and lacked clinical variables such as medication adherence and smoking.

"Another area that needs investigation is the potential danger of using fluoroquinolones in patients with genetic forms of aortopathy, such as Marfan syndrome, Loeys-Dietz syndrome, and familial thoracic aortic aneurysm and dissection. In the setting of inherited defects in aortic wall integrity, fluoroquinolones might exacerbate aortic degeneration and trigger complications, even in patients who have not yet developed aortic dilatation," according to LeMaire.

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