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PubMed1986

Comparative antiarrhythmic actions of encainide and its major metabolites.

The local anesthetic, antiarrhythmic, and acute toxicologic properties of the O-demethyl (ODE), 3-methoxy-O-demethyl (MODE) and N-demethyl (NDE) analogs of encainide (E) were compared with those of parent drug in several models. In the mouse chloroform-induced fibrillation model, the order of antiarrhythmic potency was ODE greater than E greater than MODE greater than NDE. The acute LD50 values for ODE, E, MODE and NDE in mice were 22.6, 38.1, 43.6 and 81.1 mg/kg, i.p. Based upon the toxic/therapeutic ratio in mice, ODE appeared to have the greatest margin of safety and MODE the least; E and NDE were intermediate. In dogs with ouabain-induced tachyarrhythmias, the converting doses of encainide, ODE, MODE and NDE were 0.67, 0.15, 0.39 and 1.1 mg/kg, i.v., respectively. The ODE and MODE metabolites thus appear to be more potent on a mg basis, but both have shorter durations of action than the parent compound. Antiarrhythmic activity in this model was best reflected by plasma drug level (Cp) rather than dose of drug administered. Antiarrhythmic onset Cp associated with encainide (244 ng/ml), ODE (77 ng/ml), MODE (164 ng/ml) and NDE (851 ng/ml) have been identified in this anesthetized dog model. In conscious dogs previously subjected to Harris two-stage coronary artery ligation, the minimal effective doses of encainide were 0.5 mg/kg i.v. and 1 mg/kg orally. For ODE and MODE the minimal effective doses were 0.25 and 0.19 mg/kg injected i.v., respectively, and 0.5 and 0.38 mg/kg given orally. By both routes, encainide had the shortest onset, longest duration and most consistent profile of sustained antiarrhythmic effects. Antiarrhythmic activity did not correlate with local anesthetic potency of either encainide or its metabolites. The data are consistent with the hypothesis that the metabolites of encainide may contribute to and/or be responsible, at least in part, for the persistent antiarrhythmic actions observed clinically following chronic administration of the parent drug in patients.

Anesthetics, Local↗
PubMed1979

Clinical electrophysiologic effects of encainide, a newly developed antiarrhythmic agent.

Encainide is a newly developed antiarrhythmic agent. With the use of intracardiac electrophysiologic techniques, its effects on the cardiac conduction system were examined in 10 patients with coronary artery disease. Five patients received 0.6 and five received 0.9 mg/kg body weight of encainide intravenously over 15 minutes. Plasma concentration, heart rate, blood pressure and conduction intervals (A-H, H-V, QRS and Q-T) were measured before, during and after encainide infusion. In addition, sinus nodal recovery time, Wenckebach cycle length, and atrial, atrioventricular (A-V) nodal and right ventricular refractory periods were measured before and after encainide infusion. The average peak plasma concentration was 0.49 +/- 0.35 microgram/ml (mean +/- standard error of the mean). Encainide significantly prologned H-V and QRS intervals in all patients by an average of 31 +/- 7 and 18 +/- 9 percent (standard deviation) (P less than 0.001), respectively. A minimal increase in the Q-T interval was also observed after encainide infusion (2 +/- 9 percent, P less than 0.01), but no significant changes were noted in heart rate, blood pressure, A-H interval, corrected sinus noal recovery time, Wenckebach cycle length or refractory periods of the atrium, A-V node or right ventricle. It is concluded that encainide significantly prolongs conduction in the His-Purkinje system without affecting conduction or refractoriness of other parts of the cardiac conduction system in man.

Aged↗
PubMed1990

Encainide--an updated safety profile.

The safety of encainide has been evaluated using retrospective analyses of the Bristol-Myers Supraventricular and Ventricular Arrhythmias data base and of the Post-Marketing Adverse Experience Report data and prospective analyses of the Cardiac Arrhythmia Suppression Trial (CAST), the Cardiac Arrhythmia Pilot Study (CAPS), and the Ventricular Tachycardia/Heart Disease and Boston studies. CAST, a randomized, placebo-controlled study in patients with a history of myocardial infarction with asymptomatic or minimally symptomatic ventricular arrhythmias, showed that sudden death or nonfatal cardiac arrest occurred more frequently on encainide (24/418, 5.7%) than on placebo (7/416, 1.7%). The highest sudden death/cardiac arrest rates were found in patients with a left ventricular ejection fraction of less than 0.30, those with a ventricular premature beat count of more than 50/hr and those with a myocardial infarction of more than 90 days. Similar sudden death/cardiac arrest rates were seen in the flecainide-treated group of the study but not in the moricizine-treated group. A retrospective analysis of the data collected from a similar cohort of patients in the Bristol-Myers data base showed a 1-year cumulative incidence of 10.2% in patients with a history of myocardial infarction. A retrospective analysis of mortality data in patients with supraventricular arrhythmias (301 patients) showed this to be slightly lower than in a matched sample of the general U.S. population. The sudden death mortality in the Ventricular Tachycardia/Heart Disease and Boston studies were similar to those reported with other antiarrhythmic agents. Abnormal laboratory findings caused four patients to be discontinued prematurely, but there have been no reported cases of any blood dyscrasias. Thus, there are currently no data showing that patients with symptomatic reentry supraventricular and life-threatening ventricular arrhythmias are at increased risk with encainide therapy. Encainide should be reserved for those patients who are refractory or intolerant to other antiarrhythmic agents. Encainide is not indicated in patients with symptomatic ventricular arrhythmias and structural heart disease. In patients without structural heart disease and symptomatic ventricular arrhythmias, the benefit and risks of encainide therapy should be carefully considered before it is prescribed.

Anilides↗
PubMed1986

Acute intravenous and long-term oral hemodynamic effects of encainide.

The short- and long-term hemodynamic effects of encainide, a new class IC antiarrhythmic agent, were studied in 25 patients (mean age 61 +/- 11) with complex symptomatic ventricular arrhythmia and left ventricular dysfunction. Ninety-two percent had previous myocardial infarction and 8% had dilated cardiomyopathy. Seventy-five percent had congestive heart failure, class III or IV, according to the New York Heart Association. All patients underwent a nuclear ventriculogram performed at least 3 days after discontinuing previous antiarrhythmic drugs. Nuclear ventriculograms were repeated 1 to 6 weeks later while the patients were receiving therapeutic doses of encainide ranging from 75 to 300 [corrected] mg/day. Nuclear ventriculograms were also repeated after 6 months or 1 year of encainide therapy in 16 of these patients. Encainide did not have significant effects on heart rate, blood pressure, left ventricular ejection fraction, systolic or end-diastolic volumes. None of the patients showed a worsening of congestive heart failure during encainide therapy. These results compare favorably with those of other class I antiarrhythmic agents. A review of published reports on the hemodynamic effects of intravenous encainide shows it to have a mild but statistically significant dose-related depressant effect on cardiac function. This effect, however, appears to be no different from that of other newer class I agents.

Administration, Oral↗
PubMed1988

Treatment of ectopic atrial arrhythmias and premature atrial complexes in adults with encainide.

Few studies of the antiarrhythmic effects of encainide have included patients with primary atrial tachycardias and premature atrial contractions (PACs). In this review, 11 patients with primary atrial tachycardia and 10 patients with symptomatic PACs were abstracted from all studies known to have been performed. These patients had been shown to be highly resistant to prior antiarrhythmic treatments. Intravenous encainide terminated a primary atrial tachycardia in 4 of 4 patients, 3 of whom had an incessant arrhythmia, and oral encainide was effective or partially effective in 6 of 10 patients treated for an average of 2.9 years with a mean dosage of 156 mg/day. Intravenous encainide was effective or partially effective in 8 of 10 patients with symptomatic PACs, and oral encainide was effective or partially effective in 6 of 9 patients treated for an average of 1.8 years with a mean dosage of 114 mg/day. The median number of PACs per hour on Holter recording was reduced from a baseline rate of 1,139/hour to 166/hour at 3 to 5 months of treatment (p = 0.001). Adverse effects were modest. The mechanism of action of encainide in these arrhythmias appears to be depression of ectopic pacemaker activity.

Adolescent↗
PubMed1991

Increased risk of death and cardiac arrest from encainide and flecainide in patients after non-Q-wave acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial. CAST Investigators.

This report examines whether in the Cardiac Arrhythmia Suppression Trial death and cardiac arrest from encainide, flecainide and moricizine during the titration phase and from encainide and flecainide during the follow-up phase were related to presence (Q-wave acute myocardial infarction [Q-AMI]) or absence (non-Q-AMI) of pathologic Q waves. In all, 2,371 patients (70% with Q-AMI, 26% with non-Q-AMI, and 4% unknown) entered the titration phase, starting 117 +/- 163 days after index AMI and lasting for an average of 21 days. For the titration phase, no significant differences existed between Q-AMI and non-Q-AMI patients for death and cardiac arrest rate, ventricular premature complex suppression rate, and nonrandomization rate. A total of 1,498 patients entered the follow-up phase of an average of 10 months (starting 129 +/- 158 days after the index AMI), and were randomized to encainide or flecainide, or their matching placebos. In the placebo group, non-Q-AMI patients had a significantly lower rate of death and cardiac arrest than Q-AMI patients (1.0 and 4.6%, respectively; p = 0.04). Encainide and flecainide significantly elevated death and cardiac arrest rate in both non-Q-AMI patients (8.7%, p less than 0.01) and Q-AMI patients (7.8%, p = 0.04). The relative risk for encainide or flecainide over placebo in the non-Q-AMI patients was 8.7, which was significantly higher than 1.7 observed for the Q-AMI patients (p = 0.03). None of the baseline characteristics had any significant interaction with encainide or flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Complexes, Premature↗
PubMed1989

Resolution of enantiomers of the antiarrhythmic drug encainide and its major metabolites by chiral derivatization and high-performance liquid chromatography.

Commercially available chiral columns were unable to provide adequate resolution of enantiomers of the antiarrhythmic drug encainide or its major metabolites. The homochiral derivatizing agent, (-)-menthyl chloroformate, was found to react at the tertiary piperidine nitrogen of racemic encainide providing two menthyl carbamate diastereomers. The individual diastereomers could be separated with baseline resolution on normal-phase high-performance liquid chromatography on a silica column. Structures of the derivatives were confirmed by electron impact mass spectrometry and 1H NMR spectroscopy. The method was adapted for the chiral analysis of the major metabolites of encainide. The limit of sensitivity for racemic encainide was 10 ng on column and it was possible to detect a mixture containing (+)- and (-)-encainide in a ratio of 1:99. Preliminary studies indicated that (-)-encainide was O-demethylated to a greater extent than the (+)-enantiomer by rat liver microsomes.

Anilides↗
PubMed1986

Effect of encainide and flecainide on chronic ectopic atrial tachycardia.

In the treatment of chronic ectopic atrial tachycardia, standard antiarrhythmic therapy has been shown to be ineffective in the majority of patients. The intravenous and oral effects of two class IC antiarrhythmic drugs, encainide and flecainide, in five patients with chronic ectopic atrial tachycardia were studied using exercise testing, 24 hour long-term electrocardiography and programmed electrical stimulation. All patients had been treated unsuccessfully with at least four antiarrhythmic drugs. In two patients tachycardia was persistent, and in three patients tachycardia occurred intermittently for more than 12 hours/day. Intravenous encainide and flecainide at doses ranging from 0.3 to 2.0 mg/kg and from 0.5 to 1.5 mg/kg body weight, respectively, terminated atrial ectopic tachycardia in all patients. Oral encainide, 150 to 225 mg/day, completely suppressed ectopic atrial activity in four patients during a mean follow-up period of 8 +/- 3 months. In the remaining patient encainide markedly reduced the number of episodes of tachycardia. In three patients encainide had to be withdrawn because of intolerable side effects. These patients were well controlled with oral flecainide, 200 to 300 mg/day, without side effects. On the basis of these results, the efficacy of encainide and flecainide in the treatment of chronic ectopic atrial tachycardia appears to be not drug-specific but rather a general class IC property.

Adult↗
PubMed1986

Encainide disposition in patients with renal failure.

The antiarrhythmic agent encainide undergoes extensive presystemic biotransformation to form O-desmethylencainide (ODE) and 3-methoxy-ODE (MODE) in subjects who exhibit the extensive metabolizer (EM) phenotype for debrisoquin 4-hydroxylation. These metabolites contribute significantly to the overall antiarrhythmic activity and are extensively excreted in the urine. Therefore, the effects of renal impairment on the disposition of encainide and its metabolites were studied in seven EM patients with renal failure and compared with those in eight healthy normal subjects of the same phenotype. After a single dose of encainide, its systemic and oral clearances were significantly lower and its elimination t1/2 was shorter in patients with renal failure than in healthy volunteers. This shortening was explained by a significant reduction in steady-state volume of distribution in renal failure. After chronic dosing to steady state, quantitatively similar changes were seen. Chronic oral dosing produced 80% higher levels of ODE (the most pharmacodynamically active metabolite) and 167% higher levels of MODE as compared with healthy volunteers. The prolongations in ECG intervals were similar in the two groups despite the higher encainide dose in the normal subjects. In conclusion, patients with renal failure will require lower doses of encainide because of both reduced encainide clearance and increased accumulation of active metabolites.

Acute Kidney Injury↗
PubMed1991

Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.

BACKGROUND AND METHODS: In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo. RESULTS: Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty. CONCLUSIONS: There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

Actuarial Analysis↗
PubMed1988

Long-term efficacy of oral encainide in frequent and repetitive ventricular arrhythmias.

The short- and long-term efficacy of oral encainide was studied in 14 patients with chronic high-frequency ventricular arrhythmias and in 14 patients with chronic frequent episodes of non-sustained ventricular tachycardia (NSVT). Encainide efficacy was assessed during a dose-titration period and in a 36-month follow-up also studying the drug effects on routine haematologic data and left ventricular function (LVF). During dose-titration, encainide caused a 78.3% decrease in the average hourly frequency of isolated PVC and a 96.1% reduction in NSVT episodes in the two groups of patients. On follow-up (11 patients in each group) the mean percentage reductions were 95.1% in isolated PVC and 99.7% in NSVT episodes. Encainide did not impair LVF as showed by the comparison of echocardiographic fractional shortening before and after 12 months of treatment. Minor adverse effects of encainide were dose-related visual disturbances in two patients. A major adverse effect was the appearance of sustained VT in one NYHA class IV patient. Oral encainide effectively reduces the frequency of PVC and NSVT, it does not impair left ventricular function and it is associated with infrequent minor side effects. Uncommon, but severe, side effects may appear in patients with marked impairment of left ventricular function.

Adolescent↗
PubMed1987

Electrophysiologic and clinical effects of intravenous and oral encainide in patients with Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation.

The electrophysiologic effects of encainide were studied in 10 patients with Wolff-Parkinson-White syndrome after intravenous (1 mg kg-1 in 60 minutes) and oral administration of two dose regimens (75 and 150 mg daily). Under control conditions atrial fibrillation (AF) with a rapid ventricular response was induced in all patients and atrioventricular reciprocating tachycardia (AVRT) in 9 patients. After intravenous encainide AF was no longer induced in 3/9 patients; in 3 of the remaining the accessory pathway (AP) was totally blocked and in the others the shortest RR interval increased from 213 +/- 6 to 297 +/- 91 ms and the mean RR interval from 293 +/- 39 to 362 +/- 79 ms. The lower dose of oral encainide prolonged the shortest RR interval from 206 +/- 24 to 273 +/- 64 ms and the mean RR interval from 280 +/- 48 to 368 +/- 52 ms in 6 patients; in 2 cases no preexcited beats were recorded and in 1 AF was not inducible. After the higher dose of oral encainide AF was still inducible in 7/8 cases; in 3 the AP was blocked and in the others the shortest and mean RR intervals increased from 202 +/- 30 to 280 +/- 24 ms and from 276 +/- 59 to 436 +/- 80 ms, respectively. After intravenous encainide antegrade conduction over the AP was blocked in 4/9 patients and the antegrade effective refractory period (ERP) was prolonged in another 4. Oral encainide blocked AP conduction in 4 cases and prolonged ERP considerably in the others.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Long-term follow-up of incessant supraventricular tachycardia treated with oral encainide.

The long-term follow up (32 to 44 months, mean 37 months) of 9 patients with incessant supraventricular tachycardia treated with oral encainide is reported. During that follow up period, 1 patient developed an 'escape' phenomenon to encainide and incessant supraventricular tachycardia recurred in spite of increasing doses of encainide. Two patients required electrical fulguration of the bundle of His because of inability to control incessant supraventricular tachycardia. One patient discontinued treatment without suffering from recurrences of the arrhythmia. In 6 of the original 11 patients treated with oral encainide, antiarrhythmic efficacy persisted after a mean of 3 years. No additional long-term side effects developed. It is concluded that the antiarrhythmic efficacy of oral encainide in incessant supraventricular tachycardia persists long-term, although some patients may develop an 'escape' phenomenon to encainide while others develop spontaneous cure of tachycardia.

Administration, Oral↗
PubMed1991

Use-dependent actions and effects on transmembrane action potentials of flecainide, encainide, and ethmozine in canine Purkinje fibers.

The Cardiac Arrhythmia Suppression Trial implicated flecainide and encainide as proarrhythmic in a specific clinical setting, whereas ethmozine was not. The purpose of the present study was to attempt to understand the cellular basis for these different drug effects by comparing the actions on transmembrane action potential characteristics and onset and offset of use-dependent block in canine Purkinje fibers using standard microelectrode techniques. All drugs caused qualitatively similar changes on action potential characteristics: reduction of action potential amplitude and the maximum rate of depolarization (Vmax) as well as acceleration of repolarization. Ethmozine and the orthodemethyl (O-D) metabolite of encainide had greater effects at all concentrations studied than encainide or flecainide. Although ethmozine induced greater use-dependent reduction of Vmax than flecainide or encainide, it also showed faster onset and recovery from use-dependent block. The time constant of recovery from use-dependent block for O-D encainide was about 5 times that of the parent compound. The rates of onset and recovery from use-dependent block for ethmozine were similar to those reported for class IA drugs like disopyramide and much slower than class IB drugs like lidocaine. The faster on and off rates of ethmozine when compared to flecainide and encainide in this study may provide the basis for the differing effects of these drugs on conduction in situ and their proarrhythmic actions.

Action Potentials↗
PubMed1992

Effects of ibutilide on spontaneous and induced ventricular arrhythmias in 24-hour canine myocardial infarction: a comparative study with sotalol and encainide.

The electrophysiologic and antiarrhythmic effects of ibutilide, sotalol, and encainide were compared in dogs 24 h after myocardial infarction. Ibutilide (0.03 to 0.3 mg/kg i.v.) prevented the induction of ventricular arrhythmias in 100% of the dogs that had demonstrated inducible ventricular arrhythmias prior to treatment. This antiarrhythmic action was associated with significant increases in ventricular refractoriness and monophasic action potential duration. Sotalol (1.0 to 10.0 mg/kg i.v.) increased the ventricular refractory period and monophasic action potential duration and prevented the induction of ventricular arrhythmias in 75% of the dogs that demonstrated inducible ventricular tachyarrhythmias at baseline. Although 10 mg/kg of sotalol was required to prevent the initiation of ventricular tachycardia, this dose produced marked cardiovascular depression and hypotension in 50% of the dogs tested. Neither ibutilide nor sotalol significantly decreased the incidence of spontaneous ventricular arrhythmias. The class IC agent encainide (0.3 to 3.0 mg/kg i.v.) was successful in preventing the induction of ventricular arrhythmias in only 20% of the dogs tested. However, in contrast to ibutilide and sotalol, encainide significantly reduced spontaneous arrhythmias. Atrial and ventricular refractoriness were significantly increased only after the highest dose of encainide tested (3.0 mg/kg). Over the dose ranges studied, the relative efficacy for prevention of pacing-induced ventricular arrhythmias was ibutilide greater than sotalol much greater than encainide. For suppression of spontaneous ventricular arrhythmias, the relative efficacy was encainide much greater than ibutilide = sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Sinus node dysfunction and sudden cardiac death following treatment with encainide.

Encainide, a class Ic drug, is generally thought of as having little effect on sinus node function. In this article, we present the clinical course and electrophysiological findings of a patient who had cardiac arrest after 1 week of encainide therapy for ventricular extrasystoles. No ventricular tachyarrhythmias were induced during programmed ventricular stimulation (baseline study and while receiving encainide therapy). Prior to encainide therapy, sinus node function was normal, but clinical observations after admission for cardiac arrest and subsequent electrophysiological study revealed that encainide had caused striking impairments in sinus node function. During a 6-month follow-up without antiarrhythmic drug treatment, this patient has had an uneventful course. We concluded that encainide can cause severe and life-threatening sinus node dysfunction.

Anilides↗
PubMed1989

Antiarrhythmic efficacy, clinical electrophysiology, and pharmacokinetics of 3-methoxy-O-desmethyl encainide (MODE) in patients with inducible ventricular tachycardia or fibrillation.

In most patients, the clinical effects of therapy with encainide are mediated by the generation of the active metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide (MODE). Data from in vitro and animal studies have indicated that MODE has electrophysiologic and pharmacokinetic features that make its further evaluation desirable; in earlier studies, we found that MODE suppressed chronic high-frequency nonsustained ventricular arrhythmias at plasma concentrations of 50-160 ng/ml. We now report the clinical electrophysiology, antiarrhythmic activity, and pharmacokinetics of MODE in 17 patients with inducible ventricular tachyarrhythmias (VTs) in whom programmed electrical stimulation was performed before drug administration and after one or two sequences of loading and maintenance infusions of MODE. Because the relation between plasma concentration and effect had been incompletely defined, a dose-titration approach was adopted: available pharmacokinetic data were used to construct loading and maintenance infusion regimens that were predicted to attain low plasma concentrations in initial patients while higher infusion rates were evaluated in subsequent patients. MODE prevented VT induction in three of 17 patients and VT cycle length was increased by greater than or equal to 100 msec in a further seven of 17; most responses to MODE occurred at plasma concentrations greater than 556 ng/ml (greater than 1 SD above mean plasma MODE during encainide therapy). Response to MODE did not predict subsequent response to oral therapy with encainide. MODE increased intracardiac conduction times, QT intervals during atrial and ventricular pacing, and right ventricular effective refractory periods (RVERP); changes in RVERP were most prominent at rapid pacing rates, while changes in intracardiac conduction were rate-independent at cycle lengths between 400 and 600 msec. Plasma MODE concentrations measured during electrophysiology study correlated well with those predicted by the pharmacokinetic simulations (r = 0.91, p less than 0.001). Serial plasma sampling after programmed electrical stimulation indicated a minimum MODE elimination half-life of 8.2 +/- 5.4 hours. Side effects were confined to three instances of asymptomatic conduction system depression in subjects with latent conduction system disturbances. We conclude that MODE slows intracardiac conduction, delays repolarization, and can suppress or substantially modify inducible VT. Moreover, it was only with the adoption of the dose-titration strategy that we were able to safely demonstrate that plasma MODE concentrations higher than those routinely observed during encainide therapy were required to substantially alter cardiac electrophysiology.

Adult↗
PubMed1990

Inefficacy and proarrhythmic effects of flecainide and encainide for sustained ventricular tachycardia and ventricular fibrillation.

OBJECTIVE: To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias. DESIGN: Patients were treated with encainide or flecainide. Efficacy was assessed by comparing the results of programmed ventricular stimulation while patients received therapy with the results while they were drug free. SETTING: The electrophysiology laboratory of the University of California at San Francisco. PATIENTS: Forty-nine patients with spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation for whom treatment with at least one class IA antiarrhythmic agent had failed. INTERVENTIONS: Patients were treated with encainide, 35 to 50 mg three or four times daily, or flecainide, 100 to 200 mg twice daily. RESULTS: Arrhythmia worsened early in 5 of 16 patients receiving encainide and 3 of 33 patients receiving flecainide. Patients with poor left ventricular function were more likely to exhibit proarrhythmia (P = 0.02). Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia. CONCLUSION: Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function.

Adult↗