Classification of antiarrhythmic agents: electropharmacologic basis and clinical relevance

Only antiarrhythmic agents with class I activity prolong QRS duration The most marked QRS prolongation is produced by the IC agents, followed by IA and IB. This is consistent with the kinetics of interaction of each of these three subclasses with the sodium channel. Amiodarone's effect on QRS duration is between that of the IB and IA agents consistent with its tau rec of 1.5 seconds. Moricizine's effects on QRS duration are more marked than would be expected from its tau rec of 2.6 seconds but may be explained by the slow onset of inactivation block. The greatest efficacy in VPC suppression is exhibited by the class IC agents and amiodarone. Although amiodarone and sotalol are included in class III, amiodarone has marked class IB activity and sotalol is a more potent beta-adrenergic blocker. The disparate effects of these two drugs in suppressing VPCs may be explained by the class I action of amiodarone. It is surprising that drugs within each subclass correlate at all in VPC suppression in view of the marked heterogeneity of mechanisms potentially producing VPCs. Antiarrhythmic agents with class III activity seem to be the most effective in patients with inducible sustained ventricular tachyarrhythmias. Except for the class I agents with class III activity, that is, IA agents, all class I agents are effective in only 10% to 15% of patients with inducible ventricular tachycardia. The discordance between sotalol and amiodarone is unexplained. As expected, the most marked prolongation of ventricular tachycardia cycle length occurs with the class IC agents, followed by class IA and IB. At the rapid rates of the ventricular tachycardia, frequency-dependent sodium channel block occurs even with the "fast IB" drugs, and ventricular tachycardia cycle length is prolonged.