Fluoroquinolones and Cardiac Valve Regurgitation Risk
What is the association between fluoroquinolone (FQ) use and increased risk of mitral and aortic regurgitation?
In recent years, adverse events such as retinal detachment, tendon rupture, and aortic aneurysms and dissection have been attributed to FQ use, with more recent case reports of valvular prolapse. The in vitro ability of FQ to damage connective tissue and collagen has been proposed as the causative mechanism. This study sought to assess the association between FQ use and increased risk of mitral and aortic regurgitation.
First, a disproportionality analysis was performed using the Food and Drug Administration (FDA)’s Adverse Events Reporting System (FAERS) database, which includes all reported prescription drug-related adverse events from 2004-2018. Authors compared valvular regurgitation reports linked to FQs versus those linked to all other drugs to generate reporting odds ratios (RORs) and corresponding confidence intervals (CIs).
Next, a nested case-control study was performed using the US PharMetrics Plus health claims database, applying International Classification of Diseases (ICD)-9 and -10 codes related to mitral and aortic valve regurgitation. Conditions that independently increased the risk of valvular regurgitation (e.g., endocarditis, rheumatic fever, strep throat) and several other disorders (e.g., tricuspid valve disease, myocarditis, and mitral stenosis) were excluded prior to identification of cases. Each case was matched to 10 control subjects based on age, follow-up time, and index date. The authors calculated risk ratios (RRs) for FQ use relative to two other antibiotics, amoxicillin and azithromycin. Cases were divided into current (within 30 days), recent (31-60 days) or past use (61-365 days). Finally, a conditional logistic regression model was used to adjust crude RRs for age, gender, atrial fibrillation, coronary artery disease, stroke, and exposure to certain drugs (e.g., phentermine).
There were 102 reported FQ-associated valvular regurgitation adverse events (AEs) and 6,099 reports with other drugs in the FAERS database. Based on these numbers, the authors reported an ROR of 1.45 (95% CI, 1.2-1.77), although they do not specify the number of nonvalvular AEs implicit in this calculation. RORs vary significantly for different FQs from a high of 2.87 (gatifloxacin) to a low of 0.73 (moxifloxacin). In the case-control study, there were 12,502 cases of valvular regurgitation (9,774 mitral regurgitation and 2,390 of aortic regurgitation) and approximately 125,000 control subjects. The adjusted RR with current FQ use was 2.40 (95% CI, 1.82-3.16) when compared to amoxicillin and 1.75 (95% CI, 1.34-2.29) when compared to azithromycin. The adjusted RRs were less significant for recent use and close to 1.0 for past use of FQs relative to both amoxicillin and azithromycin.
This nested case-control study shows a stronger association between current FQ use and valvular regurgitation than that seen with two other antibiotics. This accompanies a disproportionality analysis done on an FDA database, which shows a ROR >1 for FQs as a whole, albeit with disparity between individual class members.
This article adds valvular regurgitation to the list of cardiovascular conditions potentially associated with FQ use. Mining of FDA and health claims databases allows for large sample size, but introduces the possibility of unmeasured confounders and limits conclusions regarding cause and effect. Guidelines regarding the use of FQs in patients with risk factors for or history of valvular regurgitation must await further, prospective studies.
Keywords: Antibiotic Prophylaxis, Aortic Valve Insufficiency, Atrial Fibrillation, Azithromycin, Cardiac Surgical Procedures, Connective Tissue, Coronary Artery Disease, Fluoroquinolones, Heart Valve Diseases, Mitral Valve Insufficiency, Pharmaceutical Preparations, Phentermine, Risk Factors, Secondary Prevention, Stroke
< Back to Listings