Current Antiarrhythmic Drugs. Reorientation in drug therapy to control cardiac arrhythmias continues to evolve in the wake of ongoing refinements in techniques and indications for radiofrequency ablation and the use of implantable devices for atrial and ventricular arrhythmias. The role of sodium channel blockers continues to be questioned, and data from clinical trials indicate that the use of this class of drugs should be limited to control symptoms in patients who have arrhythmias and either no or minimal heart disease. The decline in the use of sodium channel blockers has led to greater use of beta blockers and complex Class III agents, such as sotalol and amiodarone, as both primary therapy and adjunctive therapy with implantable defibrillators in patients with cardiac disease of varying degrees of ventricular dysfunction. Success with these Class III agents in the context of their side effects has led to the synthesis and characterization of compounds with simpler ion channel-blocking properties. The need for such compounds stemmed from the observation that atrial fibrillation (AF) as an arrhythmia is, for the most part, still not amenable to curative therapy by interventional procedures. The isolated block of the rapid component of the delayed rectifier current (I-Kr) has been found to have either a neutral (e.g.,dofetilide) or deleterious (e.g., d-sotalol) effect on mortality in survivors of myocardial infarction. Thus, the objective of drug development should be the appropriate match between the substrate and an antiarrhythmic drug. The so-called pure Class III agents have been shown to have beneficial antifibrillatory effects in patients with AF. They are effective in inducing acute chemical conversion, preventing paroxysmal AF, and maintaining sinus rhythm in patients with persistent AF restored to sinus rhythm with DC cardioversion. AF is a complex arrhythmia, undoubtedly a result of multifaceted derangement of atrial ionic currents. Attention has therefore focused on newer compounds that have the propensity to block more than one ion channel. Examples of such agents are tedisamil and azimilide, the latter having been studied extensively in humans. It is the first of the Class III agents that block both components (I-Kr and I-Ks) of the delayed rectifier current, which results in a spectrum of electrophysiologic properties that includes lack of rate or use dependency in terms of effect on repolarization and refractoriness of atrial and ventricular myocardium. Available but unpublished clinical data indicate that azimilide may be effective over a wide range of tachycardia cycle lengths with a low incidence of torsades de pointes. In these respects, its properties, at least in terms of its use in AF, resemble those of amiodarone. However; the drug has little or no effect on AV conduction, which precludes the modulation of ventricular response in patients relapsing to AF.
