title: 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 anti-arrhythmic therapy in patients with benign and potentially lethal ventricular premature complexes (VPCs), 28 patients with initial efficacy with moricizine (greater than 75% suppression of baseline mean VPCs/hr and greater than 90% suppression of repetitive VPCs) were prospectively followed for 1 to 56 (mean +/- standard deviation 25 +/- 17) months. Patients were examined during baseline placebo, anti-arrhythmic drug therapy and intermittent pulsed-placebo 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine, St. Louis University Medical Center, Missouri 63110-0250.
authors.forename: H L
authors.initials: HL
authors.lastname: Kennedy
authors.forename: M K
authors.initials: MK
authors.lastname: Sprague
authors.forename: S M
authors.initials: SM
authors.lastname: Homan
authors.forename: S M
authors.initials: SM
authors.lastname: Seiler
authors.forename: R D
authors.initials: RD
authors.lastname: Wiens
authors.forename: D L
authors.initials: DL
authors.lastname: Janosik
authors.forename: R M
authors.initials: RM
authors.lastname: Redd
authors.forename: T A
authors.initials: TA
authors.lastname: Buckingham
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D004361:Drug Tolerance; D005069:Evaluation Studies as Topic; D006801:Humans; D016293:Moricizine; D010640:Phenothiazines / Q000097:blood / Q000627:therapeutic use; D010919:Placebos; D011336:Probability; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D010640:Phenothiazines; D010919:Placebos; D016293:Moricizine