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The pharmacological therapy of ventricular arrhythmias in patients with unsuccessful or not feasible catheter ablation and contraindication or inefficacy to amiodarone and beta-blockers, is controversial. The present study investigated the effectiveness and tolerability of mexiletine in patients with recurrent ventricular arrhythmias and ischaemic heart disease, when the conventional antiarrhythmic therapy failed. We enrolled all consecutive patients with unsuccessful/not feasible catheter ablation and ineffective/contraindicated amiodarone or beta-blockers, which started the mexiletine treatment for refractory ventricular tachycardia (VT) or ventricular fibrillation (VF) between January 2010 and January 2020. The primary endpoint was the total number of VT/VF episodes after the beginning of mexiletine therapy. The 2 secondary endpoints were the overall number of therapies released by implantable cardioverter-defibrillators (ICDs) and the discontinuation of the pharmacological therapy. The events occurring during the mexiletine treatment period were compared with those observed in a matched duration interval before the initiation of therapy. Thirty-four consecutive patients (27 males, 79.4%; mean age 74.0 ± 9.5 years) with ischaemic heart disease were finally analysed. The median of mexiletine treatment was 26.5 months (interquartile range: 18.75–38.25 months). After the mexiletine start, VT/VF episodes and ICD interventions significantly decreased (respectively: 74 vs 33 episodes,  p  = 0.002; 116 vs 52 interventions,  p  = 0.02) in comparison with a matched period without mexiletine. Six patients (13.9%) discontinued the treatment because of severe side effects. The treatment period following the mexiletine start was associated with a significant reduction of ventricular arrhythmias. The rate of side effects requiring dosage reduction or interruption was not neglectable.

Mexiletine for ventricular arrhythmias in patients with chronic coronary syndrome: a cohort study