Researchers found an association between the use of fluoroquinolone antibiotics and increased risk for aortic and mitral regurgitation, according to study results published in the Journal of the American College of Cardiology.

The aim of this study was to assess the relationship between the use of fluoroquinolone antibiotics and the rate of valvular regurgitation according to the hypothesis that fluoroquinolone antibiotics are more likely to damage the connective tissue in the aortic and mitral valve apparatus. The study was completed in 2 steps. The first step was a disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System to identify cases of fluoroquinolone-related valvular regurgitation and any nonfluoroquinolone-related valvular regurgitation cases from 2004 to 2018.

The second step was a case-control study using the US PharMetrics Plus database to quantify valvular regurgitation secondary to fluoroquinolone antibiotic use. Researchers identified cases of valvulopathy after a fluoroquinolone prescription and then matched the cases to control participants according to time, age, and index date. Researchers included patients prescribed amoxicillin or azithromycin in the analysis as a control for confounding variables.


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They grouped all antibiotic prescription use according to time from regurgitation episode as current (within the last 30 days), recent (between 31 days and 60 days), and past (61 days to 365 days).

For the disproportionality analysis, investigators used 102 cases of fluoroquinolone-related valvular regurgitation and 6099 cases of nonfluoroquinolone-related valvular regurgitation. Overall, there was a total reporting odds ratio of 1.45 (95% CI, 1.2-1.77).

There were 12,502 cases of valvulopathy and 125,020 control participants used for the case-control study. For the current users of fluoroquinolone antibiotics, the adjusted risk ratio (aRR) was 2.4 (95% CI, 1.82-3.16) when compared with amoxicillin and 1.75 (95% CI, 1.34-2.29) when compared with azithromycin.

For the recent users of fluoroquinolone antibiotics, the aRR was 1.47 (95% CI, 1.03-2.09) when compared with amoxicillin, and 1.37 (95% CI, 0.95-1.98) when compared with azithromycin. For past users of fluoroquinolone antibiotics, the aRR was comparable with both amoxicillin and azithromycin.

When the researchers assessed the type of valvular regurgitation, current users of fluoroquinolone antibiotics had an aRR for mitral regurgitation of 2.25 (95% CI, 1.77-2.87) when compared with amoxicillin and 1.75 (95% CI, 1.37-2.22) when compared with azithromycin.

Current users of fluoroquinolone antibiotics had an aRR for aortic regurgitation of 2.24 (95% CI, 1.3-3.87) when compared with amoxicillin and 1.9 (95% CI, 1.06-3.42) when compared with azithromycin. Past users of fluoroquinolone antibiotics had a comparable aRR between both types of valvular regurgitation and amoxicillin and azithromycin usage.

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Limitations of this study included the lack of ability to assess causal relationships with disproportionality analyses, the potential for other unmeasured confounding variables in the case-control study, and generalizability of results to all US populations, as databases used for study included only patients who had private health insurance.

The researchers concluded that the study showed “an association between oral fluoroquinolones and an increased risk of mitral and aortic regurgitation. As such, it might be prudent to consider antibiotics that are chemically distinct to [fluoroquinolones] in patients with a previous history of valvular regurgitation who require antibacterial therapy.”

Reference

Etminan M, Sodhi M, Ganjizadeh-Zavareh S, Carleton B, Kezouh A, Brophy JM. Oral fluoroquinolones and risk of mitral and aortic regurgitation. J Am Coll Cardiol. 2019;74(11): 1444-1450.