Risk Factors and Markers for Flecainide Toxicity in Clinical Practice

Background: Flecainide is an antiarrhythmic drug effective against both ventricular and supraventricular arrhythmias. However, its use is limited by concerns over potential severe toxicity. This study aims to characterize flecainide toxicity in current clinical practice and identify its associated risk factors and markers. Methods: We conducted a retrospective, single-centre analysis of all patients admitted to Brugmann Hospital, Brussels, Belgium during 2014-2022 who received flecainide and had a follow-up period of a minimum of 3 months. We compared baseline characteristics of patients who developed toxicity to flecainide with those of patients who did not. Results: A total of 300 patients were included; 39 (13%) developed flecainide toxicity, with a mortality rate of 18% among these cases. Several risk factors and markers were associated with toxicity, including baseline sinus bradycardia, chronic kidney disease, hepatic cirrhosis, drug interactions, left ventricular ejection fraction during treatment, baseline QT interval duration, and prolongation of QRS and QT intervals during treatment. Baseline ischemic or structural heart disease, with or without left ventricular dysfunction, did not emerge as a risk factor for toxicity. Conclusions: Flecainide toxicity remains of consequence as it is associated with significant morbidity and mortality. Classic contraindications, such as left ventricular dysfunction or structural heart disease, were not associated with an increased risk of toxicity. Instead, metabolic retention factors (chronic kidney disease, hepatic cirrhosis, or drug interactions) and preclinical markers of overdose (sinus bradycardia, left ventricular ejection fraction under treatment, baseline QT interval, and prolongation of QRS and QT intervals during treatment) increased the likelihood of toxicity.