Adverse reaction profiles of long-term class I antiarrhythmic therapy in patients with potentially malignant ventricular arrhythmias

The long-term outcome of 698 patients discharged from the hospital following initiation of successful class I antiarrhythmic agents for potentially malignant ventricular arrhythmias was studied retrospectively. The study population consisted of patients with underlying cardiac disease with moderate to high frequency ventricular ectopy (paired ventricular premature complexes and/or nonsustained ventricular tachycardia), with or without related symptoms. Prior to initiation of antiarrhythmic therapy, each patient received a 12-lead electrocardiogram, on-line continuous computer arrhythmia monitoring, a 2D/M-mode echocardiogram, and a complete blood count. Patients and/or their primary care physicians were contacted at three to four month intervals following discharge concerning the patient's tolerance to antiarrhythmic therapy. At each follow-up interval patients had a repeat history and physical examination, a 12-lead electrocardiogram, and were asked to respond to an adverse reaction questionnaire. Repeat 2D/M-mode echocardiograms, antiarrhythmic blood levels, complete blood counts, and 24-hour ambulatory electrocardiographic recordings were obtained at the discretion of the primary care physician. Distribution of patients was as follows: quinidine group, 148; procainamide group, 178; disopyramide group, 42; tocainide group, 151; mexiletine group, 117; flecainide group, 49; and encainide group, 13. Reasons for antiarrhythmic agent discontinuation were classified as due to side effects; lose of efficacy; death; non-drug-related reasons; and due to all causes combined. Rates of discontinuation were significantly higher for procainamide, disopyramide, flecainide, and encainide than for tocainide, mexiletine, and quinidine (P < 0.05) due primarily to a higher incidence of discontinuation due to side effects (P < 0.05). Differences in rates of discontinuation of the study drugs due to loss of efficacy, death, and non-drug-related causes were not statistically significant. Until evidence is available to demonstrate that antiarrhythmic therapy in patients with potentially malignant ventricular arrhythmias reduces mortality from sudden death, the risk of prescribing these agents must be seriously considered. The selection of agents with the least potential for the development of serious side effects, both acutely and during long-term therapy, remains an important consideration in antiarrhythmic drug therapy.

Duke Scholars

Author Michael Hugh Sketch Jr. Medicine, Cardiology