Antiarrhythmic Drug Therapy for Suppression of Ventricular Arrhythmia: Experience with 122 Patients Treated for Two Years

Abstract

Although there are many reports of the short-term effectiveness of antiarrhythmic drugs for suppression of ventricular ectopic depolarizations, there are less data available on the long-term use of these drugs. We treated 122 patients for up to 2 years with antiarrhythmic drugs for suppression of frequent ventricular ectopic depolarizations. The percent suppression of ventricular ectopic depolarizations and nonsustained ventricular tachycardia for each drug was determined at 1, 3, 6, 12, 18, and 24 months of therapy. Among 33 patients treated with flecainide, the mean suppression of ventricular ectopic depolarizations (average of all data during 24 months) was 93 +/- 17% and of nonsustained ventricular tachycardia was 97 +/- 7%. In 27 patients treated with encainide, the mean suppression of ventricular ectopic depolarizations was 88 +/- 18% and of ventricular tachycardia was 95 +/- 16%. Among 26 patients treated with propafenone, the mean suppression of ventricular ectopic depolarizations was 77 +/- 32% and of ventricular tachycardia was 93 +/- 15%. For the 20 patients treated with moricizine, the mean suppression of ventricular ectopic depolarizations was 62 +/- 35% and of ventricular tachycardia was 90 +/- 14%. Among 16 patients treated with amiodarone, the mean suppression of ventricular ectopic depolarizations was 92 +/- 14% and of nonsustained ventricular tachycardia was 99 +/- 3%. In 54 of the 122 patients (44%), the study drug was stopped during 2 years of therapy because of death (2 sudden, 2 unwitnessed and 6 noncardiac), side effects (21 patients), lack or of loss of efficacy (13 patients), and noncompliance (10 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac effects of quinidine on guinea‐pig isolated perfused hearts after in vivo quinidine pretreatment

“…In contrast with the vascular eects, the electrophysiological and inotropic eects of quinidine on myocardial tissue were not signi®cantly dierent in the pretreated group than in controls. These ®ndings substantially agree with the persistence of therapeutic ecacy during longterm treatment observed in some clinical studies with class 1a and 1c drugs (McCollam et al, 1989;Salerno et al, 1990), but dier from those previously obtained by other authors (Du et al, 1985;Kennedy et al, 1989;Capucci et al, 1990;Le Coz et al, 1992;Boriani et al, 1993). It could be argued that either the duration of quinidine pretreatment or the steady state plasma concentrations attained were not adequate for tolerance to develop.…”

“…In all these therapeutic studies it is unclear whether loss or decrease in therapeutic eectiveness was due to spontaneous variability of cardiac arrhythmias or to a true pharmacological tolerance. Indeed, other clinical investigations (McCollam et al, 1989;Salerno et al, 1990) did not ®nd any decline in the therapeutic ecacy of class I antiarrhythmic drugs during long term treatment. A molecular basis for the tolerance hypothesis has recently been provided by an experimental study in rats (Taouis et al, 1991), which showed the development of up-regulation of cardiac sodium channels (dosedependent and reversible upon drug withdrawal) over a 6-day treatment with the Na channel blocker, mexiletine.…”

Wenxin Keli for the Treatment of Arrhythmia—Systems Pharmacology and In Vivo Pharmacological Assessment

“…However, the progress is not satisfactory ( Weiss et al, 2015 ; Camm, 2017 ). Though ion channels drug discovery has greatly evolved for nearly half a century, the drugs cause adverse reactions ( Frommeyer and Eckardt, 2016 ), such as thyroid dysfunction, pulmonary fibrosis, and anaphylaxis ( Salerno et al, 1990 ; Johannes et al, 2010 ; John et al, 2012 ). In recent years, ablation-guided electrophysiology and implantable cardioverter defibrillators have been widely used in arrhythmia treatment, achieving gratifying results ( McKenna et al, 2019 ).…”

Combination Formulation of Tetrodotoxin and Lidocaine as a Potential Therapy for Severe Arrhythmias

“…Severe ventricular tachycardia or fibrillation can be fatal, and this occurs when the heart cannot pump blood at a normal pace to provide effective cardiac output. Emergency treatment of ventricular arrhythmias is a challenge, since current medications can lead to side effects such as thyroid dysfunction, pulmonary fibrosis, and anaphylaxis [1][2][3]. Therefore, better medication is needed.…”