Oral fluoroquinolones and risk of aortic or mitral regurgitation: a nationwide nested case-control study

Abstract

Aims Reports have suggested an increased risk of aortic and mitral regurgitation associated with oral fluoroquinolones (FQs) resulting in a safety warning published by the European Medicines Agency (EMA). However, these findings have not yet been replicated. Methods and results Using Danish administrative registers, we conducted a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. Cases were defined as the first occurrence of aortic or mitral regurgitation. Exposure of interest was the use of oral FQs. Hazard ratios (HRs) with 95% confidence intervals (95% CI) 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. We identified 38 370 cases of valvular regurgitation with 1 115 100 matched controls. FQ exposure was not significantly associated with increased rates of aortic or mitral regurgitation (HR 1.02, 95% CI 0.95–1.09) compared with penicillin V users. Investigating the cumulative defined daily doses (cDDD) of FQs yielded similar results with no significant association between increasing FQ use and valvular regurgitation (e.g. HR 1.08, 95% CI 0.95–1.23 for cDDD >10 compared with cDDD 1–5). These results were consistent across several analyses including a cohort of patients with hypertension and using a case definition based on valvular surgical interventions. Conclusions In a nationwide nested case-control study, FQs were not significantly associated with increased rates of valvular regurgitation. Our findings do not support a possible causal connection between FQ exposure and incident valvular regurgitation.

Overview of Side-Effects of Antibacterial Fluoroquinolones: New Drugs versus Old Drugs, a Step Forward in the Safety Profile?

“…However, in a recent study, Strange et al [ 82 ] demonstrated that increased valvular regurgitation rates are not significantly associated with oral FQs. Therefore, more studies must confirm or deny the link between FQs and increased aortic and mitral regurgitation.…”

“…The study included 51,898 patients across three databases from the USA [ 174 ]. Additionally, another recent study (nationwide nested case-control) conducted in Denmark did not find a significant association between FQs regimens and the increased rates of valvular regurgitation [ 82 ]. The Therapeutic Goods Administration received no reports of aortic aneurysms or dissection associated with FQs regimens from Australia until the date of the FDA warning and the EMA’s PRAC recommendation [ 90 ].…”

Y3+@CdTe quantum dot nanoprobe as a fluorescence signal enhancement sensing platform for the visualization of norfloxacin

“…2 However, due to the overuse of antibiotics and their poor biodegradability, NOR residues are present in water, meat, dairy products, honey and other foods, leading to bacterial resistance, which may cause metabolic disorders, liver damage, joint pain and pose a threat to human health. [3][4][5] NOR has been explicitly banned in the US since 2014. 6 The Chinese Ministry of Agriculture has banned its use in animal husbandry since December 31, 2016.…”

Association Between Use of Fluoroquinolones and Risk of Mitral or Aortic Valve Regurgitation: A Nationwide Cohort Study

“…One recent in vitro study further suggested that fluoroquinolones might damage the integrity of collagen in the heart valves 14 . However, the few real‐world studies that have examined the association between fluoroquinolones and heart valvular diseases have produced inconsistent findings 15–17 . One Norwegian case report showed that use of oral ciprofloxacin, one of the commonly used fluoroquinolones, at a dose of 750 mg for 2 days, may lead to an acute effect of cardiac decompensation and aortic valve damage 15 .…”