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.