Evolving role of sotalol in the management of ventricular tachyarrhythmias

Sotalol is a unique compound with several potential antiarrhythmic mechanisms, including beta blockade (class II activity), action potential duration prolongation (class III activity), and possibly reduction of QT dispersion. In recent years, trials such as the Cardiac Arrhythmia Suppression Trial (CAST) and the Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial reported disappointing results with the use of class I agents in the management of ventricular arrhythmias in patients with coronary artery disease. These results have led to increased interest in class III antiarrhythmic agents, including sotalol. Sotalol is effective in suppressing ventricular premature complexes as well as nonsustained and sustained ventricular tachyarrhythmias. The interaction between sotalol and implantable cardioverter-defibrillators (ICDs) is generally favorable. As is the case with other antiarrhythmic drugs, there is no placebo-controlled trial assessing the effect of sotalol on mortality. It is not known if sotalol is more effective than placebo, conventional beta blockade, amiodarone, or ICDs in reducing mortality from life-threatening ventricular arrhythmias. In addition, the optimal method of selecting patients for sotalol therapy has yet to be determined. The safety profile of sotalol has been well established in > 3,000 patients worldwide. Proarrhythmia occurs in approximately 4% of patients, and torsades de pointes occurs in approximately 2.5%. The majority of episodes of torsades de pointes occurs within 3 days of commencing sotalol therapy, and the risk of torsades de pointes increases sharply at dosages > 320 mg daily. It is recommended that initiation of sotalol therapy or dosage increases be performed in a monitored setting. Overall, only 1% of patients enrolled in clinical trials of sotalol discontinued therapy as a result of drug-related congestive heart failure. However, these trials have excluded patients with poor left ventricular systolic function and/or overt heart failure. The optimal management of these patients, who are at greatest risk of sudden cardiac death, and of patients with substrates other than coronary artery disease remains to be elucidated.