Natural history of potentially lethal ventricular arrhythmias in patients treated with long-term antiarrhythmic drug therapy

Abstract

To examine the natural history of long-term antiarrhythmic therapy in patients with benign and potentially lethal ventricular premature complexes (VPCs), 28 patients with initial efficacy with moricizine (>75% suppression of baseline mean VPCs/hr and >90% suppression of repetitive VPCs) were prospectively followed for 1 to 56 (mean ± standard deviation 25 ± 17) months. Patients were examined during baseline placebo, antiarrhythmic drug therapy and intermittent pulsedplacebo reexamination periods. The mean VPCs of all patients at baseline entry were 233 ± 47 VPCs/ hr, and after moricizine therapy 14 ± 4 VPCs/hr. Follow-up demonstrated that antiarrhythmic efficacy decreased to 75% at 12 months and to 62% at 24 months. Loss of antiarrhythmic drug efficacy most commonly occurred as a “transient” event (10 patients [36%]), and efficacy was spontaneously reestablished without a change in antiarrhythmic therapy. In contrast, increased dose titration of moricizine was necessary to reestablish antiarrhythmic suppression efficacy in 4 patients (14%), and 4 patients (14%) lost antiarrhythmic drug responsiveness during follow-up. Spontaneous decrease in baseline VPCs resulted in discontinuation of antiarrhythmic therapy in 3 patients, and increase in baseline VPCs was associated with a loss of antiarrhythmic response in 2 patients. Late proarrhythmic effects (2 patients, 7%), delayed side effects necessitating drug withdrawal (6 patients, 21%) and medical events (4 patients, 14%) occurred during 56 months of follow-up. Individual serum moricizine levels remained in the therapeutic range throughout the study and did not correlate with changes in antiarrhythmic efficacy. Both the development of time-dependent changes in spontaneous variability of VPCs and the occurrence of late clinical and arrhythmic events confound the evaluation of long-term antiarrhythmic drug therapy.