Antiarrhythmic medications have been available for nearly 100 years and remain a mainstay in the management of atrial fibrillation (AF). Goals of therapy with the use of these drugs include a reduction in the frequency and duration of episodes of arrhythmia as well an emerging goal of reducing mortality and hospitalizations associated with AF. The use of these drugs has been limited by both proarrhythmic and noncardiovascular toxicities as well as often modest antiarrhythmic efficacy. Despite these limitations, antiarrhythmic drugs remain widely prescribed for the management of symptomatic AF, and a host of new antiarrhythmic drugs are in various stages of clinical development. This review will focus primarily on antiarrhythmic drug use in patients with AF in the absence of significant structural heart disease or congestive heart failure.
How to evaluate a new antiarrhythmic drug: The challenge of sudden cardiac death.- How to evaluate a new antiarrhythmic drug: The challenge of sudden cardiac death.- Pre-Clinical Evaluation of a New Antiarrhythmic Agent.- Relationships between effects on cardiac electrophysiology and antiarrhythmic efficacy.- What animal models should be used to define antiarrhythmic efficacy: acute dog models?.- Description of chronic canine myocardial infaction models suitable for the electropharmacologic evaluation of new antiarrhythmic drugs.- Non-canine animal models for evaluating antiarrhythmic efficacy General Group Discussion: Animal Models.- Defining the pharmacodynamics and pharmacokinetics of new antiarrhythmic drugs General Group Discussion: Pharmacology.- Chronic Studies in Patients with Non-Hemodynamically Significant Ventricular Arrhythmics.- How should Holter monitoring analysis be performed?.- Long-term ambulatory electrocardiographic recording in the determination of efficacy of new antiarrhythmic agents.- Evaluation of antiarrhythmic drugs. Should the Lown classification be used as a measure of efficacy?.- General Group Discussion: Holter Monitoring.- Study Designs: Chronic Patients.- New means of evaluating antiarrhythmic drugs.- Parallel or crossover designs in evaluation of antiarrhythmic therapy.- General Group Discussion: Study Designs: Chronic Patients.- Remarks: J. Richard Crout, Director, Bureau of Drugs Food and Drug Administration.- Acute Studies in Patients with Hemodynamically Significant Significant Ventricular Arrhythmias.- Acute drug testing as a part of a systematic approach to antiarrhythmic drug therapy.- What is the role of electrophysiology in drug testing? General Group Discussion: Electrophysiology.- What should the study design be to test new antiarrhythmic drugs in patients with acute myocardial infarction, digitalis toxicity and other acute problems General Group Discussion: Study Designs in Acute Patients.- Special Considerations.- What baseline electrophysiologic data should be obtained (plus discussion).- Assessment of the hemodynamic and inotropic effects of antiarrhythmic drugs (plus discussion).- Evaluation of drug treatment in supraventricular arrhythmias (plus discussion).- How should long-term safety of a new antiarrhythmic drug be defined (plus discussion).- How should one manage emergency drug requests and their data (puls discussion).- How does one evaluate and use outside U.S.A. data in the new drug application (plus discussion).