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At least 271 records · Page 15Linked to original sources
PubMed1990

New aspects of the clinical use of anti-arrhythmia agents with special reference to acute therapy of ventricular tachycardia (lidocaine vs. ajmaline).

Antiarrhythmic treatment is based on the hypothesis that ventricular premature beats (VPBs), in the presence of underlying cardiac disease and impaired ventricular function, may predispose to sudden cardiac death. The effectiveness of treatment, however, has not been proven. For acute treatment of paroxysmal ventricular tachycardia, on comparison of the effectiveness of lidocaine and ajmaline, some new aspects have been rendered. VENTRICULAR PREMATURE BEATS (VPB): Isolated VPBs can be found in 40 to 75% of healthy subjects; if their number is substantial, investigation is warranted. For VPBs with subjective symptoms, beta-receptor blockers or specific antiarrhythmic agents, if necessary in combination, may be given. In several studies it has been shown that the prognosis of patients with frequent and complex VPBs, that is couplets and salvos, without heart disease is not compromised. In one long-term study over an average of 6.5 years, sudden death was observed in only one of 70 subjects who had 566 VPBs/24 hours, 60% additionally couplets and 26% salvos in the Holter ECG. Accordingly, treatment for the sake of prognosis is not warranted. For patients with mitral valve prolapse or only mildly impaired ventricular function and asymptomatic arrhythmias, treatment is not necessary since it has not been shown to be beneficial. Coronary artery disease is the most frequent cause of ventricular arrhythmias and sudden death. In numerous studies in patients after myocardial infarction, a relationship has been recognized between frequent and complex VPBs and overall mortality as well as sudden death. Particularly at risk are patients with very frequent and complex VPBs with additional impairment of ejection fraction to less than 30 to 40% but this group only accounts for 10% of patients after infarction. Only in one interventional study, carried out with aprindine, there was a significant reduction in overall mortality from 12.5 to 7.8% with an adverse reaction rate, however, of 21%. In high-risk patients with a low ejection fraction and numerous, complex VPBs as well, in a further study with aprindine, after one year, there was no decrease in overall mortality as compared with the placebo group. The cause for the insufficient effectiveness of the antiarrhythmic agents in various interventional studies has been attributed to a limited number of patients, rigid dosing regimens, inadequate suppression of VPBs and a high incidence of adverse reactions. In the multicenter, randomized, placebo-controlled CAST study with newer substances, a total of 2309 patients with essentially asymptomatic VPBs at a rate of more than 6/hour and an ejection fraction less than 55% or 40% admitted more than 90 days after infarction, respectively, were followed from six days to two years after myocardial infarction to determine if the significant suppression of VPBs in patients with coronary artery disease with antiarrhythmic agents leads to a reduction in arrhythmia-associated deaths. Flecainide, encainide and moricizine led to a significant suppression of VPBs in 75% of the patients. After an average of ten months, the rate of arrhythmia-induced deaths of 4.5% in those treated with encainide or flecainide was significantly higher than the 1.2% observed in the placebo group. These results appear attributable to a proarrhythmic effect of the class IC drugs during long-term treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Ajmaline↗
PubMed1990

Moricizine: a new class I antiarrhythmic.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of the Class I antiarrhythmic agent moricizine hydrochloride are reviewed. Moricizine is chemically similar to the phenothiazines but does not appear to block dopaminergic receptors. Its major electrophysiologic actions are a concentration-dependent decrease in maximum rate of phase 0 depolarization; increased rates of phase 2 and 3 repolarization, decreased action potential duration, and decreased effective refractory period. Moricizine causes a dose-related prolongation of the PR interval and of AV nodal, infranodal, and intraventricular conduction times but has little effect on ventricular repolarization. The antiarrhythmic and electrophysiologic effects are not correlated with plasma concentrations of the drug or its metabolites. Moricizine reduces the occurrence of ventricular premature contractions (VPCs), couplets, and nonsustained ventricular tachycardia. It appears to suppress symptomatic nonsustained ventricular tachycardia, sustained ventricular tachycardia, and ventricular fibrillation or flutter. Moricizine appears to be as effective as quinidine and more effective than disopyramide, propranolol, and imipramine but less effective than flecainide and encainide at reducing VPCs. Moricizine continues to be evaluated in the Cardiac Arrhythmia Suppression Trial, which was designed to assess the long-term benefit of arrhythmia suppression in patients with left ventricular dysfunction after myocardial infarction. Moricizine seems to be better tolerated than quinidine, disopyramide, and imipramine and to have less proarrhythmic potential than flecainide or encainide. Noncardiac adverse effects include dizziness, nausea, and headache. Cimetidine appears to decrease moricizine clearance, and decreased theophylline clearance has been reported in subjects given moricizine. The usual adult dosage of moricizine hydrochloride is 600-900 mg/day given in three divided doses; an every-12-hour regimen may be used in some patients. Because of the risk of proarrhythmic effects, indications are limited to treatment of documented life-threatening arrhythmias. Moricizine will compete with other agents as first-line therapy for life-threatening arrhythmias.

Arrhythmias, Cardiac↗
PubMed1988

SC-36602, a new antiarrhythmic agent: comparison of its cardiovascular profile with that of other antiarrhythmic drugs.

The cardiovascular profile of SC-36602, a new class 1A/1B antiarrhythmic agent, was compared to those of disopyramide, lidocaine, mexiletine, flecainide, encainide, lorcainide, and quinidine. These drugs were compared at their respective canine antiarrhythmic doses in a hemodynamic evaluation using anesthetized dogs. In another test using anesthetized dogs, the cardiovascular effects of cumulative doses of SC-36602 were assessed. The direct negative inotropic potential of each drug was also determined using isolated cat papillary muscles. In the hemodynamic study, SC-36602 and quinidine did not cause significant myocardial depression, measured as a decrease in the maximal first derivative of the left ventricular pressure. (Heart rate and diastolic filling pressure were not controlled in order to mimic clinical conditions). SC-36602, mexiletine, flecainide, and quinidine increased heart rate. SC-36602 and mexiletine caused a small increase in mean arterial pressure, whereas disopyramide and quinidine decreased it. Disopyramide was the only drug studied that increased left ventricular end-diastolic pressure. SC-36602, quinidine, and mexiletine increased index of cardiac effort. Disopyramide caused a decrease in the latter. Disopyramide, flecainide, encainide, and lorcainide lengthened the ECG intervals. Cumulative intravenous doses of SC-36602 up to 50 mg/kg produced significant decreases in mean arterial pressure, increases in heart rate, and increases in P-R and QRS intervals of the ECG relative to placebo-matched controls. SC-36602 had the least direct negative inotropic action of the drugs studied, as measured in isolated papillary muscles. These data suggest SC-36602, when compared to the other antiarrhythmic drugs studied, has the least amount of hemodynamic side-effects at its antiarrhythmic dose.

Animals↗
PubMed1989

Acute effects of combination of IB and IC antiarrhythmics for the treatment of ventricular tachycardia.

There are limited data on the effects of Class IB and IC antiarrhythmic drug combination for the treatment of ventricular tachycardia. The present study evaluated this combination in 12 patients who had sustained ventricular tachycardia (SuVT) during programmed electrical stimulation (PES) and failed IC antiarrhythmic therapy. Following combination of lidocaine and a IC agent (7 with encainide and 5 with flecainide), two had no inducible ventricular tachycardia (VT) and one had nonsustained VT (NSVT). In seven of nine patients who still had SuVT, the mean VT cycle length increased 40 +/- 25 msec post combination compared to IC antiarrhythmic therapy. Seven patients who had a favorable response to the initial combination (less than 10 beats of NSVT, or greater than or equal to 10 beats of VT with a greater than 100 msec increase in cycle length compared to baseline and no hemodynamic compromise) were then placed on IC + oral IB agent (5 with mexiletine, 2 with tocainide). Similar effects on VT inducibility and cycle length were observed following the oral combination. In conclusion, the addition of lidocaine to IC therapy produced favorable effects on induced ventricular tachycardia in 58% of patients compared to IC agent alone. Also, a positive PES response to lidocaine and IC therapy corresponded to a similar positive response when either mexiletine or tocainide was substituted for lidocaine.

Anilides↗
PubMed1990

Reassessment of benefit-risk ratio and treatment algorithms for antiarrhythmic drug therapy after the cardiac arrhythmia suppression trial.

The Cardiac Arrhythmia Suppression Trial (CAST) has led to serious reconsideration of both the benefit-risk ratio of antiarrhythmic drug therapy and the appropriate therapeutic approach to various cardiac arrhythmias. Class IC drugs, such as encainide and flecainide, should not be used to treat asymptomatic postinfarction arrhythmias. Furthermore, because the CAST raises serious questions about the concept of treating asymptomatic but "potentially malignant" (prognostically important) arrhythmias guided by ambulatory monitoring, the prophylactic use of any of the antiarrhythmic agents (except beta blockers) must be considered inappropriate and potentially harmful until otherwise established by specific clinical trials. For prophylaxis of malignant ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation), treatment may still begin with standard agents in classes IA, IB, or both, preferably guided by electrophysiologic testing alone or in combination with noninvasive testing. Class IC therapy may be most useful in those patients in this group who do not have such high-risk characteristics for proarrhythmia as a history of multiple myocardial infarctions (MIs), congestive heart failure, or low ejection fraction. Amiodarone is moderately effective for treating these arrhythmias but is reserved as second- or third-line therapy because of its potential organ toxicity. Sotalol, a beta blocker with class III activity, is often effective and relatively well tolerated in these patients and may become a preferred drug when approved. For symptomatic but nonmalignant ventricular arrhythmias, a more conservative approach is more appropriate than in the past, with therapy reversed for those with debilitating symptoms. An initial trial of beta blockade is often appropriate before class I agents are considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1987

Newer antiarrhythmic drugs in children.

Our experience with the use of five new antiarrhythmic drugs for treating life-threatening arrhythmias in children will be briefly reviewed. Prevention of recurrent episodes of atrial flutter with digoxin and local anesthetic antiarrhythmic drugs often is only moderately successful, benefiting 65% of patients. Amiodarone is particularly useful for those patients who cannot be controlled on this regimen. We caution that the heart rate be monitored carefully when therapy with amiodarone is initiated in patients likely to have sick sinus syndrome. We have found mexiletine useful for controlling significant ventricular arrhythmias in patients with congenital heart disease. Likewise, 79% (11 of 14) of patients with ventricular tachycardia treated with amiodarone were well controlled. However, the range of disease categories (congenital heart disease, myocarditis, cardiomyopathy) in which amiodarone is effective is much broader than for mexiletine. Although other investigators have used amiodarone successfully for controlling supraventricular tachycardia in the Wolff-Parkinson-White syndrome or secondary to concealed accessory AV connections, we recommend surgical ablation. Propafenone has significantly improved our ability to control postoperative JET. Although JET is self-limited in duration and spontaneously remits, it frequently produces life-threatening hemodynamic compromise in the postoperative setting. Propafenone slows the ventricular rate into a range in which AV sequential pacing may be instituted. Generally, after 24 to 72 hours, the patient may be quickly weaned from propafenone. Chronic incessant supraventricular tachycardia (SVT) is frequently associated with a dilated cardiomyopathy. The two most common mechanisms of incessant SVT are PJRT and AET. We have found encainide and ethmozine extremely effective in suppressing tachycardia episodes in PJRT and AET, respectively. Medical therapy has been associated with few side effects.

Adolescent↗
PubMed1982

Clinical and electrophysiologic findings in patients with repetitive monomorphic ventricular tachycardia and otherwise normal electrocardiogram.

Natural history, structural substrate, electrocardiographic and electrophysiologic characteristics and therapy were evaluated in 18 patients who demonstrated repetitive ventricular tachycardia, defined as repeated episodes of ventricular tachycardia that had a uniform QRS configuration and normal sinus-conducted QRS complexes between the episodes of tachycardia. The patients were young (mean age 37 years) and frequently had a long history of arrhythmias before this evaluation; only two patients has a history of syncope and six were completely asymptomatic. Fourteen patients had no evidence of underlying structural heart disease, three had mitral valve prolapse and one had congestive cardiomyopathy. Episodes of ventricular tachycardia tended to occur in clusters over a 24 hour electrocardiographic recording period. Repetitive ventricular tachycardia was induced in two of nine patients by programmed electrical stimulation, and in seven patients incremental atrial and ventricular pacing suppressed spontaneous arrhythmia. In the one patient whose tachycardia was induced by incremental ventricular pacing there was an inverse relation between pacing cycle length and the interval from the last paced complex to the first complex of ventricular tachycardia, indicating there was overdrive suppression. At a follow-up time of 0.5 to 8 years no patient had died or had worsening of symptoms. Encainide completely eliminated episodes of ventricular tachycardia during acute treatment in five of six patients tested. Seven patients received no antiarrhythmic therapy and the arrhythmia appeared to have spontaneously resolved in four of these patients. Repetitive ventricular tachycardia appears to have distinct clinical and electrophysiologic characteristics. In this series the arrhythmia had a good prognosis and often required no treatment. The electrophysiologic features are consistent with a mechanism of automaticity.

Adolescent↗
PubMed1983

Importance of metabolites in antiarrhythmic therapy.

The presence of metabolites with pharmacologic activity can produce unanticipated drug efficacy or toxicity. This is particularly true during treatment with drugs that have narrow therapeutic-toxic ratios, such as the antiarrhythmic agents. The presence of active metabolites can often be inferred from variability in the relation between pharmacologic effect and steady-state plasma concentrations of the parent drug. Moreover, metabolites may ordinarily be unimportant but can accumulate to therapeutic (or toxic) levels in disease states such as congestive heart failure, renal failure and hepatic failure. Further characterization of the contribution of such metabolites during treatment requires direct evaluation of their pharmacology in vitro, in animal models and, if indicated, in man. Procainamide and its active metabolite N-acetylprocainamide provide the best and most complete example of this sequence of observations. Other drugs, including quinidine, disopyramide, verapamil and the investigational agents encainide and lorcainide, have active metabolites for which pharmacologic activity is less well-defined. Further studies in this area will help reduce the frequency of antiarrhythmic drug adverse effects, make successful therapy more frequent, and perhaps allow insights into structure-activity relations.

Acecainide↗
PubMed1986

Effects of congestive heart failure on the pharmacokinetics and pharmacodynamics of antiarrhythmic agents.

Changes in the pharmacokinetics of antiarrhythmic agents should be expected in patients with congestive heart failure (CHF). The direction of the changes, however, is not always predictable. The volume of distribution is often decreased by as much as 40%, and loading doses should, therefore, be appropriately reduced. Drug clearance may also be diminished due to decreased blood flow to the liver and kidneys, as well as decreased hepatic drug-metabolizing activity. Infusion rates should similarly be lowered to avoid toxicity. However, decreases in both volume of distribution and clearance may result in little, if any, change in elimination half-life, despite higher plasma concentrations. On the other hand, the elimination half-life of antiarrhythmic agents that have a large volume of distribution and are highly cleared by the liver may be twice as long in patients with CHF compared with normal subjects. Thus, the total daily dose of drug should also be lower in these patients. In addition, the time necessary to reach steady state is longer, so that premature dose escalation may lead to excessive drug accumulation. In terms of their pharmacodynamic effects, all antiarrhythmic agents have the potential to manifest a degree of negative inotropy, which must be anticipated as a possible side effect in patients with CHF. Some of the newer agents, such as tocainide and encainide, appear to cause only minimal myocardial depression. Other potential complications of all antiarrhythmic therapy include proarrhythmia and possible drug interactions with digitalis and diuretics.

Amiodarone↗
PubMed1987

Risk factors for the development of proarrhythmic events.

Definitions of proarrhythmia, including clinical consequence, were applied to the flecainide and encainide data bases to determine risk factors for serious proarrhythmic events or deaths. Such outcomes with flecainide were far less common for patients with benign or potentially lethal ventricular arrhythmias compared to patients with predominantly lethal ventricular arrhythmias. No deaths from proarrhythmia during flecainide therapy occurred in patients without structural heart disease. Serious proarrhythmic events and deaths were more common in patients in whom therapy was initiated in hospital than in those in whom therapy was initiated out of hospital. When the flecainide dosage for patients with lethal ventricular arrhythmias was chosen using steady-state pharmacologic principles, the occurrence of all proarrhythmic events and deaths dropped from 26% and 13% to 10% and 0%, respectively. Structural heart disease, sustained ventricular tachycardia, inpatient initiation and large-dose escalation of class IC drugs are the primary risk factors for development of proarrhythmic events.

Anilides↗
PubMed1988

Clinical predictors of arrhythmia worsening by antiarrhythmic drugs.

Aggravation of ventricular arrhythmia is a serious, potentially lethal, side effect that can occur with all antiarrhythmic agents. The purpose of this retrospective case-controlled study was to identify clinically useful parameters that would predict aggravation of arrhythmia. Patients in whom arrhythmia worsened while taking either quinidine, mexiletine or encainide were selected and matched to 2 similar patients who never developed this drug complication with any antiarrhythmic tested. A number of hemodynamic, electrophysiologic and pharmacologic parameters were compared. Only the presenting arrhythmia and a left ventricular ejection fraction less than 35% identified patients at risk for drug-induced aggravation of arrhythmia. Patients who presented with either sustained ventricular tachycardia or ventricular fibrillation were 3.4 times more likely to have arrhythmia aggravation compared with patients presenting with nonsustained ventricular tachycardia or ventricular premature beats. Patients with a left ventricular ejection fraction less than 35% were 2.2 times more likely to develop this drug complication compared with patients with an ejection fraction greater than 35%. There was no association between other clinical parameters, electrocardiographic intervals, ventricular arrhythmia density, drug dose or drug levels and aggravation of arrhythmia. In addition, drug aggravation to 1 drug did not predict its occurrence with another drug of the same class. Patients with a history of a sustained ventricular arrhythmia, especially when left ventricular dysfunction is present, are at high risk for the development of aggravation of arrhythmia.

Anilides↗
PubMed1988

Recruitment and baseline description of patients in the Cardiac Arrhythmia Pilot Study. The Cardiac Arrhythmia Pilot Study (CAPS) investigators.

The Cardiac Arrhythmia Pilot Study tested the feasibility of performing a large-scale study to evaluate the effect of therapy of ventricular arrhythmias after acute myocardial infarction (AMI). Ten clinical sites identified patients with greater than or equal to 10 ventricular premature complexes (VPCs)/hour, recorded 6 to 60 days after AMI in patients with an ejection fraction greater than 0.20. Patients were randomized to receive 1 of 5 agents: encainide, flecainide, imipramine, moricizine or placebo. Successful therapy was defined as greater than or equal to 70% suppression of VPCs and greater than 90% suppression of runs of ventricular tachycardia. Randomization to a second agent occurred if a patient did not achieve adequate suppression with the initial agent. Patients initially randomized to placebo continued to receive placebo. Patients were evaluated at 3-month intervals for the next year. Of 30,763 patients screened, 10,734 (35%) were younger than 70 years old and had a qualifying AMI. A Holter recording was obtained in 3,957 patients, of whom 871 (22%) had qualifying arrhythmias and 687 were eligible. Of the 687 eligible patients, 502 (73%) were randomized. Mean age of enrolled patients was 59 years. One-half of patients were randomized within 1 month after AMI. Mean ejection fraction was 0.45, with 175 (35%) patients having an ejection fraction less than 0.40. On baseline drug-free recording, 173 (35%) patients had less than 30 VPCs/hour; 149 (30%) between 30 and 100/hour and 180 (36%) greater than or equal to 100/hour. At least 1 run of ventricular tachycardia was seen in 172 (34%) patients. Drugs taken at baseline were similar in all groups with 116 (23%) patients taking digitalis, 161 (32%) taking diuretics, 203 (41%) taking beta blockers and 200 (40%) taking calcium antagonists. Slightly more patients, 53 (51%), randomized to flecainide were taking calcium antagonists. No significant relation was noted between baseline VPC frequency and ejection fraction, but baseline VPC frequency was correlated with heart rate, arrhythmia noted before AMI and right bundle branch block. As expected, a high ejection fraction correlated with lower peak creatine kinase values, an inferior location of the infarct and fewer signs of congestive heart failure. At baseline, at least 1 adverse symptom was volunteered by 192 (39%) patients. The most common symptoms were unusual tiredness or fatigue, heart beating fast or skipping beats or headache. In this study, over 20 age- and AMI-eligible patients were identified to obtain each randomized patient. The randomization process successfully distributed baseline variables across drug groups.

Anilides↗
PubMed1989

Congestive heart failure after acute myocardial infarction in patients receiving antiarrhythmic agents for ventricular premature complexes (Cardiac Arrhythmia Pilot Study).

The Cardiac Arrhythmia Pilot Study (CAPS) was a randomized, double-blind trial of antiarrhythmic drugs (encainide, flecainide, moricizine, imipramine and placebo) in 502 patients with an ejection fraction greater than 0.20 and at least 10 ventricular premature complexes/hour, 6 to 60 days after acute myocardial infarction. Patients were followed for 1 year and the incidence of new or worsened congestive heart failure (CHF) was evaluated. Heart failure in the 1-year follow-up was gauged by the development (in order of increasing severity) of new symptoms (grade 1), the need for a change in therapy, including addition of digitalis, addition or increase of dose of diuretics or afterload reduction agents or discontinuation of beta-blocking agents (grade 2), or by hospitalization (grade 3). Sixty-one of 502 patients (12%) required hospitalization for CHF in the 1-year follow-up. One hundred five of 403 patients (26%) in the active treatment group and 18 of 99 patients (18%) in the placebo group (difference not significant) developed CHF requiring hospitalization or a change in therapy or both. Although patients with severely impaired ejection fraction were excluded, new or worsened CHF was common in follow-up during CAPS.

Anilides↗
PubMed1990

Implications of the Cardiac Arrhythmia Suppression Trial for antiarrhythmic drug treatment.

The Cardiac Arrhythmia Suppression Trial (CAST) is a randomized, placebo-controlled, double-blind, multicenter clinical trial involving 27 centers and more than 100 hospitals in North America and Europe to test the 1-tailed hypothesis that suppression of ventricular arrhythmias in patients with left ventricular dysfunction after myocardial infarction will reduce arrhythmic death. Since April 18, 1989, the CAST is enrolling patients aged less than 80 years with greater than or equal to 6 ventricular premature complexes and left ventricular ejection fraction less than or equal to 40%. Sustained ventricular tachycardia, class IV congestive heart failure or class IV angina pectoris are exclusion criteria. During a prerandomization period, antiarrhythmic drugs are titrated to suppress ventricular arrhythmias. If greater than or equal to 80% suppression is achieved during open-label titration, patients are randomized to the effective dose or to a matched placebo. If only partial suppression (1 to 79%) is achieved, patients are eligible for a substudy that randomizes them to the best dose found during open-label titration or to placebo. The only patients not randomized to treatment are those with increased arrhythmias or drug intolerance during titration. On April 18, 1989, encainide and flecainide were removed from the CAST because these drugs increased the death rate 2.5-fold. There were no imbalances in baseline risk variables between the encainide/flecainide group and the placebo group that might explain the adverse treatment effect. There was remarkable uniformity of the adverse effect across all subgroups. There were no subgroups that benefited from treatment; all were either harmed or not evaluable.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗
PubMed1991

Prevalence, characteristics and significance of ventricular premature complexes and ventricular tachycardia detected by 24-hour continuous electrocardiographic recording in the Cardiac Arrhythmia Suppression Trial. CAST Investigators.

The prevalence, characteristics and significance of ventricular arrhythmias detected by ambulatory electrocardiography were evaluated in 1,498 patients who were randomized to encainide, flecainide or placebo in the Cardiac Arrhythmia Suppression Trial. The mean ventricular premature complex (VPC) frequency at baseline was 133 +/- 257 VPCs/hour. Nonsustained ventricular tachycardia (VT) (rate greater than or equal to 120 beats/min) was present in 22% of patients. Accelerated idioventricular rhythm (rate less than 120 beats/min) occurred in 22% of subjects. There were 63 deaths/resuscitated cardiac arrests in the active treatment (encainide/flecainide) group and 26 in the placebo group. In the treatment group mortality increased with increasing VPC frequency, (p = 0.006), whereas in the placebo group such a relation was not present. Mortality/resuscitated cardiac arrest increased in patients with greater than or equal to 2 VT episodes than in those with less than or equal to 1 episode in the active treatment group (p = 0.04). There was no significant association between VT and mortality/resuscitated cardiac arrest in the placebo group. The presence of accelerated idioventricular rhythm was not associated with increased mortality/resuscitated cardiac arrest in either the active treatment or placebo groups. However, mortality was lower in patients with accelerated idioventricular rhythm rates less than 100 beats/min than in those with rates greater than or equal to 100 beats/min (p = 0.05). Thus, in the Cardiac Arrhythmia Suppression Trial the previously described association between mortality/resuscitated cardiac arrest and ventricular arrhythmias (VPC and VT) were only observed in the active treatment group. In addition, based on the results obtained in this highly selected population, it is suggested that the definition of accelerated idioventricular rhythm should be a rate less than 100 beats/min, and at a rate greater than or equal to 100 beats/min it should be categorized as VT.

Anti-Arrhythmia Agents↗
PubMed1993

Psychosocial predictors of mortality in the Cardiac Arrhythmia Suppression Trial-1 (CAST-1).

Psychosocial variables predict the recurrence of clinical events in symptomatic patients, controlling for measures of disease severity. The Cardiac Arrhythmia Suppression Trial-1, a pharmacologic test of the arrhythmia suppression and mortality hypothesis among postmyocardial infarction patients, allowed a prospective test of the relationship of distress, perceived support, social interaction, life stress, and other variables, to mortality, adjusting statistically for ejection fraction, arrhythmia rates, and other known risk factors for coronary heart disease. Results indicated that the treatment medications, encainide and flecainide, were powerful predictors of mortality. Although the psychosocial variables were significant as univariate predictors, these variables were not significant as predictors in a multivariate model that included drug treatment. When the data analysis was restricted to patients randomized to placebo, thereby eliminating the antiarrhythmic drug effect, the level of perceived social support was a significant multivariate predictor of mortality, adjusting for measures of disease severity. The adjusted hazards ratio for a 1-point decrease in the perceived support score is equal to 1.46, based on the multivariate model.

Arrhythmias, Cardiac↗
PubMed1989

Congestive heart failure induced by six of the newer antiarrhythmic drugs.

The incidence of drug-induced congestive heart failure with several newer antiarrhythmic agents including encainide, ethmozine, lorcainide, mexiletine, propafenone and tocainide was determined in a group of 407 patients who underwent 1,133 drug tests. The incidence rate ranged from 0.7% with lorcainide to 4.7% with propafenone. Congestive heart failure was present in 167 patients (41%) who underwent 491 drug trials. Congestive failure was induced in 15 (9%) of these 167 patients and involved 19 (3.9%) of the 491 tests. Left ventricular ejection fraction was 20 +/- 8% in patients who developed congestive failure, in contrast to 39 +/- 19% in those who did not (p less than 0.001). It is concluded that each of the six antiarrhythmic drugs examined has the potential to aggravate congestive heart failure in patients with reduced left ventricular ejection fraction or a history of congestive heart failure, but the incidence rate is low and its occurrence unpredictable.

Adolescent↗
PubMed1992

The Cardiac Arrhythmia Suppression Trial: first CAST ... then CAST-II.

The Cardiac Arrhythmia Suppression Trial (CAST) was a study designed to test the hypothesis that suppression of ventricular premature complexes after a myocardial infarction would improve survival. Preliminary results showed that suppression of ventricular premature complexes with encainide and flecainide worsened survival, and the CAST continued as the CAST-II with moricizine compared with its placebo. The protocol for the CAST-II was changed to attempt to enroll patients more likely to experience serious arrhythmias. The enrollment time was narrowed to 4 to 90 days after myocardial infarction; the qualifying ejection fraction was lowered to less than or equal to 0.40; a higher dose of moricizine could be used; early titration itself was double-blind with a placebo, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. The Cardiac Arrhythmia Suppression Trial-II was subsequently terminated prematurely because 1) patients treated with moricizine had an excessive cardiac mortality rate during the 1st 2 weeks of exposure to the drug, and 2) there appeared to be little chance of showing a long-term survival benefit from treatment with moricizine. This report outlines the rationale behind the Cardiac Arrhythmia Suppression Trial and the reasons for selection of the drugs used in the CAST and CAST-II.

Anti-Arrhythmia Agents↗