Monotherapy versus Combination Therapy with Class III Antiarrhythmic Agents to Attenuate Transmural Dispersion of Repolarization: A Potential Risk Factor for Torsade de Pointes

Class III antiarrhythmic agents are used for conversion to and maintenance of sinus rhythm from arrhythmias of atrial or ventricular origin. Monotherapy can be limited by adverse events or recurrent arrhythmias. Sotalol, dofetilide, and ibutilide may induce torsade de pointes in 2-8% of patients, whereas amiodarone induces torsade de pointes in less than 1%. We reviewed the literature regarding the possible combination of class III antiarrhythmics and risk for inducing torsade de pointes. Animal studies using amiodarone plus sotalol or d-sotalol suggest that these drug combinations prolong the QTc interval but do not induce torsade de pointes. Similar data extracted from human studies of ibutilide in patients also receiving amiodarone or sotalol showed greater efficacy with combination therapy than with monotherapy, without increased torsade de pointes induction. Reduced transmural dispersion of repolarization with amiodarone and sotalol combination therapy may serve as a mechanism for reducing the risk of torsade de pointes compared with sotalol monotherapy.