Safety and toxicity of antiarrhythmic drug therapy : benefit versus risk

Although antiarrhythmic drugs remain the first and most frequently used approach to therapy for arrhythmias, there is growing concern about their safety. It has long been recognized that this class of drug is associated with frequent side effects, especially in patients with extensive underlying heart disease. However, the recent report from the Cardiac Arrhythmia Suppression Trial (CAST) has pointed out that serious toxicity may occur even in patients with less serious heart disease. There are two major reasons for antiarrhythmic therapy. First is for relief of symptoms documented to be the result of arrhythmia. Although there are few studies showing that the antiarrhythmic drugs are effective for this indication, clinical experience does confirm that this is the case. The second indication is to prevent sudden cardiac death. Although antiarrhythmic drugs are of benefit for preventing recurrent arrhythmias in those patients who have already experienced a sustained ventricular tachyarrhythmia, there are, as yet, no data that they are effective for preventing such arrhythmias in patients thought to be at high risk; for example, postinfarction patients or those with a cardiomyopathy and who have nonsustained ventricular tachycardia. Unfortunately, therapy with antiarrhythmic drugs is associated with substantial risks. Although the majority of the side effects are not serious but only "nuisance" complaints, there are more serious toxic reactions that are often idiosyncratic. Organ toxicity may occur with some of these drugs. However, the most serious problems are cardiac side effects including conduction abnormalities, worsening of congestive heart failure, and aggravation of arrhythmia.