Combination therapy with mexiletine and sotalol suppresses inherited ventricular arrhythmias in German shepherd dogs better than mexiletine or sotalol monotherapy: a randomized cross-over study.

Abstract Objectives To determine the spontaneous variability of ventricular arrhythmias (VA) and evaluate anti-arrhythmic efficacy of mexiletine, sotalol, and a mexiletine–sotalol combination in German shepherd dogs (GSD) with inherited arrhythmias. Animals, materials and methods 12 affected GSD, median age 20 weeks, received mexiletine (8 mg/kg PO q8 h), sotalol (2.5 mg/kg PO q12 h), and combination therapy for 6 days in random order. Pre- and post-treatment 24 h Holter recordings were acquired, allowing determination of VA variability and reduction in 24 h VA for each treatment. Drug concentrations during each arm were measured. Results An anti-arrhythmic effect could be inferred if ventricular premature complexes (VPC), ventricular couplets (V cpl ), ventricular tachycardia runs (VT runs ) and total ventricular ectopy (VE tot ) frequency were reduced by 61%, 97%, 98%, and 63% (1 control Holter model), by 53%, 94%, 95%, and 54% (4 control Holter model) and by 54%, 95%, 96% and 56% (3 control Holter model). Combination therapy reduced VPC and VE tot in more dogs (5/12 and 6/12) than mexiletine (1/11 and 2/11) or sotalol (2/9 and 1/9) ( p cpl , and VE tot . Sotalol monotherapy produced an increase in VT runs . Plasma mexiletine concentration was higher during combination therapy than with monotherapy. Conclusions Combination therapy reduced VPC in affected GSD. Sotalol monotherapy increased VT runs . Combination therapy increased plasma mexiletine concentrations.