Link between fluoroquinolones and aortic-aneurysm risk remains uncertain

Reuters Health Information: Link between fluoroquinolones and aortic-aneurysm risk remains uncertain

Link between fluoroquinolones and aortic-aneurysm risk remains uncertain

Last Updated: 2020-09-10

By Will Boggs MD

NEW YORK (Reuters Health) - There is no clear evidence that fluoroquinolones cause aortic aneurysms or aortic dissections, a pair of new studies with contrasting results show.

"Any increase in absolute risk of aortic aneurysm or dissection associated with fluoroquinolones appears to be very small and is unlikely to substantially alter the balance of benefits and risks of these drugs," Dr. Joshua J. Gagne of Brigham and Women's Hospital and Harvard Medical School, in Boston, told Reuters Health by email.

Based on earlier studies, the U.S. Food and Drug Administration and European Medicines Agency in 2018 warned about the potentially increased risk of aortic aneurysm or aortic dissection (AA/AD) associated with fluoroquinolone use.

Dr. Gagne and colleagues used data from IBM MarketScan, a large, commercial U.S. health-insurance-claims database, to assess this link while accounting for potential confounding by fluoroquinolone indication and bias owing to differential surveillance.

Among more than 279,000 patients with pneumonia, fluoroquinolone initiation was associated with a 2.57-fold higher incidence of AA/AD (0.03%) than was azithromycin initiation (0.01%), after propensity score matching, the researchers report in JAMA Internal Medicine.

The increased rates observed for fluoroquinolones were largely associated with AA in secondary analysis.

In contrast, among more than 948,000 patients with urinary-tract infection (UTI), the incidence of AA/AD was similar (<0.01%) following fluoroquinolone initiation and trimethoprim-sulfamethoxazole initiation.

With heart-failure hospitalization and acute myocardial infarction as negative control outcomes, there were no significant differences in these rates between fluoroquinolones and azithromycin or trimethoprim-sulfamethoxazole.

"It is unlikely that fluoroquinolones cause aortic aneurysm or dissection in generally healthy individuals when used to treat something like urinary tract infection," Dr. Gagne said. "It is possible that these drugs may contribute to risk of aortic aneurysm or dissection in medically complex patients, such as those with pneumonia. However, any increase in absolute risk is likely very small and we cannot rule out bias as an explanation for this finding."

In the other study, also in JAMA Internal Medicine, Dr. Yaa-Hui Dong of National Yang-Ming University School of Pharmaceutical Science, in Taipei City, Taiwan, and colleagues tried to estimate the risk of AA/AD associated with infections, on one hand, and fluoroquinolones versus other antibiotics among patients with the same types of infections on the other. They used data from a nationwide population-based health-insurance-claims database.

Based on 5,391 infected cases and 17,084 matched controls, they found 2.27-fold greater odds of AA/AD associated with infections after adjustment for baseline covariates, a significant risk increase.

The highest risk of AA/AD was associated with septicemia, followed by intra-abdominal infections, lower-respiratory-tract infections, UTIs, and mixed infections.

Among the 5,391 cases treated with fluoroquinolones and 53,880 matched controls, the odds of AA/AD did not differ significantly in comparisons of fluoroquinolone monotherapy versus amoxicillin-clavulanate or ampicillin-sulbactam or fluoroquinolone monotherapy versus extended-spectrum cephalosporin monotherapy.

As demonstrated in earlier studies, fluoroquinolone use was associated with a higher risk of any type of tendon rupture compared with either amoxicillin-clavulanate or ampicillin-sulbactam or extended-spectrum cephalosporins in elderly patients.

"It is important to recognize that infection per se has a potential harmful effect of AA/AD risk," Dr. Dong told Reuters Health by email. "On the contrary, fluoroquinolones do not have a greater risk of AA/AD as compared to antibiotics with similar indications."

"When there is a therapeutic indication, concerns about AA/AD should not preclude patients from necessary treatment with fluoroquinolones," Dr. Dong concluded.

Dr. Richard William Grant of Kaiser Permanente Northern California, in Oakland, who coauthored a linked editorial, told Reuters Health by email, "The study by Dong et al. suggests that the type of infection rather than the antibiotic chosen for the infection may be the factor increasing risk of AA/AD, while the study by (Gagne) et al. underscores that the way cohorts are defined may explain why sometimes the relationship is seen but other times it isn't."

"Specifically, in observational studies of existing healthcare data, AA/AD is not (generally) diagnosed without imaging studies, but imaging studies are not automatically obtained for all patients," he explained. "This raises the possibility that detection bias (i.e., are the patients who receive aortic imaging systematically different from those who don't?) may be contributing to the apparent association seen in prior studies."

"Don't be dismayed by conflicting results," Dr. Grant said. "This is the scientific process at work. As new information unfolds and studies are replicated, we often find that what we originally accepted needs to be re-evaluated. The art of medicine lies in integrating multiple sources of information, including both the ever-evolving scientific literature and the patient's own values and preferences, to arrive at a plan of care best suited for each patient."

Dr. Sonal Singh of the University of Massachusetts Medical School, in Worcester, Massachusetts, whose earlier review and meta-analysis found a small but significantly increased risk of AA/AD with fluoroquinolone use, told Reuters Health by email, "Sound clinical decisions should be made on the sum of evidence of all prior studies, and absence of evidence from studies where the time window of exposure may be too short to detect risk does not provide proof of safety."

"Given the limitations of case-control studies in databases," he said, "coupled with strong mechanistic evidence that fluoroquinolones inhibit matrix metalloproteinase involved in the degradation of the aortic wall, I would continue to exercise caution with the use of fluoroquinolones in patients with risk factors for AA/AD, such as tobacco smoking and cardiovascular disease."

SOURCE: https://bit.ly/3k1TUfQ, https://bit.ly/2ZlOpRq and https://bit.ly/329VdU2 JAMA Internal Medicine, online September 8, 2020.

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