Background: Mexiletine, a class Ib antiarrhythmic agent, is occasionally used for refractory ventricular arrhythmias (VA) when ablation or established drug therapies have failed. However, contemporary real-world data are scarce. This retrospective analysis aimed at evaluating the effectiveness and safety of mexiletine in routine clinical practice.
Methods: Demographic and clinical data of 66 consecutive patients treated with mexiletine for recurrent VA and/or electrical storm-like VA between January 2010 and October 2025 were analyzed retrospectively. The primary endpoint was VA-related rehospitalization; secondary endpoints included adverse events and time to first VA recurrence during follow-up.
Results: Mean age was 68 ± 19 years (92 % were male), 49 % had ischemic and 51 % non-ischemic cardiomyopathy. During the index hospitalization, 87.9 % of the patients remained arrhythmia-free with mexiletine (mean dose 555 mg ± 137 mg/day). During a median follow-up of 6 months (IQR 3 - 42), 19 patients (28.8 %) were rehospitalized for VT recurrence, more often in ischemic than in non-ischemic cardiomyopathy (39 % vs. 18 %, p = 0.057). No independent predictor of rehospitalization was identified in logistic regression, although ischemic etiology showed a clinically relevant trend (OR 2.4; p = 0.16). Adverse events occurred in 8 patients (12.1 %), predominantly neurological (12 %), followed by hepatic (3 %) and gastrointestinal (1.5 %) side effects; therapy discontinuation was necessary in 6 patients (9 %). Adverse events correlated with higher mexiletine doses (χ² = 15.5; p = 0.03). The median arrhythmia-free survival was 150 days (95 % CI 14–286) without difference between ischemic and non-ischemic subgroups (log-rank p = 0.97). In multivariable Cox regression, age was the only independent predictor of shorter arrhythmia-free survival (HR 1.03 [95 % CI 1.01–1.05]; p = 0.018). Neither type of cardiomyopathy, baseline LVEF, nor mexiletine dose significantly influenced outcomes.
Conclusions: In this large single-center cohort, mexiletine provided sustained antiarrhythmic efficacy over several months with an acceptable safety profile. Adverse events were infrequent but dose dependent. Increasing age was the only independent predictor of earlier VT recurrence. Further prospective studies are needed to define predictors of response and tolerance to mexiletine therapy.
