Subclassification of class I antiarrhythmic drugs: enhanced relevance after CAST

Class I antiarrhythmic drugs are traditionally divided into three subclasses--Ia, Ib, and Ic--on the grounds of differences in kinetics of interaction with the sodium channel and different effects on the duration of the action potential. The CAST study has highlighted our growing awareness of the proarrhythmic potential of this group of agents, particularly the Class Ic subgroup. Class I drugs can cause arrhythmias either by slowing conduction to critical levels, thus enhancing the possibility of reentrant arrhythmias, or in some cases by prolonging action potential duration, leading to early afterdepolarizations, which probably underlie triggered automaticity. Evidence is presented that the Class Ic compounds may be inherently more proarrhythmic than the Ib compounds, because of their lesser ability to depress ischemic myocardium selectively. Arguments are advanced for the continued use of a slightly modified subclassification of Class I antiarrhythmic drugs.