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

ObjectivesTo 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 methods12 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.ResultsAn anti-arrhythmic effect could be inferred if ventricular premature complexes (VPC), ventricular couplets (Vcpl), ventricular tachycardia runs (VTruns) and total ventricular ectopy (VEtot) 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 VEtot in more dogs (5/12 and 6/12) than mexiletine (1/11 and 2/11) or sotalol (2/9 and 1/9) (p < 0.05). The combination therapy reduced the mean number of VPC, Vcpl, and VEtot. Sotalol monotherapy produced an increase in VTruns. Plasma mexiletine concentration was higher during combination therapy than with monotherapy.ConclusionsCombination therapy reduced VPC in affected GSD. Sotalol monotherapy increased VTruns. Combination therapy increased plasma mexiletine concentrations.