Reassessment of Benefit—Risk Ratio and Treatment Algorithms for Antiarrhythmic Drug Therapy After the Cardiac Arrhythmia Suppression Trial

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Abstract
The Cardiac Arrhythmia Suppression Trial (CAST) has led to serious reconsideration of both the benefit—risk ratio of antiarrhythmic drug therapy and the appropriate therapeutic approach to various cardiac arrhythmias. Class IC drugs, such as encainide and flecainide, should not be used to treat asymptomatic postinfarction arrhythmias. Furthermore, because the CAST raises serious questions about the concept of treating asymptomatic but “potentially malignant” (prognostically important) arrhythmias guided by ambulatory monitoring, the prophylactic use of any of the antiarrhythmic agents (except beta blockers) must be considered inappropriate and potentially harmful until otherwise established by specific clinical trials.For prophylaxis of malignant ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation), treatment may still begin with standard agents in classes IA, IB, or both, preferably guided by electrophysiologic testing alone or in combination with noninvasive testing. Class IC therapy may be most useful in those patients in this group who do not have such high‐risk characteristics for proarrhythmia as a history of multiple myocardial infarctions (MIs), congestive heart failure, or low ejection fraction. Amiodarone is moderately effective for treating these arrhythmias but is reserved as second‐ or third‐line therapy because of its potential organ toxicity. Sotalol, a beta blocker with class III activity, is often effective and relatively well tolerated in these patients and may become a preferred drug when approved.For symptomatic but nonmalignant ventricular arrhythmias, a more conservative approach is more appropriate than in the past, with therapy reversed for those with debilitating symptoms. An initial trial of beta blockade is often appropriate before class I agents are considered. Class IC therapy should be avoided in patients with a history of MI (especially recent or multiple MIs), and probably in other patients with symptomatic coronary artery disease (e.g., angina, heart failure). The CAST emphasizes the need for further experimental and clinical trials and the development of new agents based on a better understanding of the overall benefit—risk ratio. As this occurs, treatment algorithms will continue to evolve.

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