Antiarrhythmic Drug Development: Classification and its Impact on Development

Antiarrhythmic therapy would be greatly facilitated if the patients most at risk of sudden death could be identified. The Lown classification of the "severity" of arrhythmias is unsatisfactory. Recent attention has been directed to dispersion of depolarization, measured by signal averaging of the terminal QRS complex, and to dispersion of repolarization, measured by comparing QT intervals in different leads of the ECG. Since the Cardiac Arrhythmia Suppression Trial (CAST) therapy with Class 1 agents, especially Class 1c, if used at all, has been diverted from attempts to suppress arrhythmias and limited to control of symptoms. Interest in new Class 3 agents has grown and several new compounds are under trial. Low-dose treatment with the original Class 3 drug, amiodarone, has yielded promising results, in that mortality and serious arrhythmias have been reduced by regimes which do not fully abolish the arrhythmia.