Fluoroquinolone Use and Aortic or Mitral Regurgitation Risk

Quick Takes

  • In a nested case-control study using Danish national registries, there was no association between fluoroquinolone use and aortic or mitral regurgitation.
  • These results were consistent across analyses that included a cohort of patients with hypertension, and using a case definition based on valvular surgical interventions as well as diagnostic codes.

Study Questions:

Is there an association between the use of fluoroquinolones (FQs) and an increased risk of aortic regurgitation (AR) or mitral regurgitation (MR)?

Methods:

Danish administrative registers were used to construct a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. The exposure of interest was the use of oral FQs. The cumulative defined daily doses (cDDD) of FQs were defined as the sum of all consumed daily doses based on all filled prescriptions within 3 years prior to the date of interest; for FQs available in Denmark during the study period, the DDD for ciprofloxacin is 1 g and the DDD for moxifloxacin is 0.4 g. Cases were defined as the first occurrence of AR or MR, with cohorts defined using diagnostic codes and using codes for surgical intervention; cases using diagnostic codes also were examined among patients with a diagnosis of hypertension, considered in an European Medicines Agency (EMA) warning to be at high risk for FQ-associated AR or MR. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were obtained by fitting time-dependent Cox regression models, with penicillin V as comparator, to assess the association between FQ use and incident valvular regurgitation.

Results:

A total of 38,370 cases of valvular regurgitation were matched with 1,115,100 controls. FQ exposure was not significantly associated with increased rates of AR or MR (HR, 1.02; 95% CI, 0.95–1.09) compared with penicillin V users. Investigating the cDDD of FQs yielded similar results, with no significant association between increasing FQ use and valvular regurgitation (HR, 1.08; 95% CI, 0.95–1.23 for cDDD >10 compared with cDDD 1–5). Results were consistent across several analyses, using case definitions based on diagnostic codes or on valvular surgical interventions, and including analysis in the cohort of patients with hypertension.

Conclusions:

In a nationwide nested case-control study, FQs were not significantly associated with increased rates of AR or MR. The authors concluded that these findings do not support a causal connection between FQ exposure and incident valvular regurgitation.

Perspective:

The use of FQs, a class of widely used antimicrobial agents with broad-spectrum activity against both gram-negative and gram-positive bacteria, has been associated with degradation of collagen and extracellular matrix, potentially increasing the risk of tendinopathy, aortic aneurysm, and aortic dissection. Based on a recent study suggesting that FQs were associated with AR and MR (Etminan M, et al., J Am Coll Cardiol 2019;74:1444-50), the EMA issued a safety concern against the use of FQs, especially in patients considered to be at high risk of regurgitant valvular heart disease (patients with hypertension or connective tissue disorders). The present nested case-control study using Danish national registries found no association between FQ use and the development of AR or MR, including analysis using a cohort of patients with a diagnosis of hypertension. Albeit existing concern for an association between FQ use and aortic pathology (Chen SW, et al., J Am Coll Cardiol 2021;77:1875-87), additional study is required to further investigate any association between FQ use and valvular regurgitation.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Valvular Heart Disease, Vascular Medicine, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and VHD, Novel Agents, Statins, Interventions and Structural Heart Disease, Interventions and Vascular Medicine, Hypertension, Mitral Regurgitation

Keywords: Aneurysm, Dissecting, Anti-Infective Agents, Aortic Aneurysm, Aortic Valve Insufficiency, Cardiac Surgical Procedures, Fluoroquinolones, Gram-Positive Bacteria, Heart Valve Diseases, Hypertension, Mitral Valve Insufficiency, Penicillin V, Prescriptions, Risk Assessment, Secondary Prevention


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