"Azimilide"

Results of a curtailed randomized controlled trial, evaluating the efficacy and safety of azimilide in patients with implantable cardioverter-defibrillators: The SHIELD-2 trial. Frequent hospital attendances in patients with implantable cardioverter-defibrillators (ICDs) result in significant morbidity and health care costs. Current drugs to reduce ICD shocks and hospital visits have limited efficacy and considerable toxicity. We evaluated the efficacy and safety of azimilide, a novel oral class III antiarrhythmic, for use in ICD patients. A total of 240 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial to evaluate the effect of oral azimilide 75 mg daily in ICD patients with previously documented ventricular tachycardia or ventricular fibrillation

, and azimilide), suggesting a compromised repolarization reserve. Finally, the selective correction of the causal variant in iPSC-CMs using CRISPR/Cas9 gene editing (isogenic control) normalized the aberrant cellular phenotype, whereas the introduction of the homozygous variant in healthy control cells recapitulated hallmark features of the LQTS disorder. The results suggest that the KCNH2 VUS may

disease.Step 3: The next step in patients who cannot take flecainide or propafenone is to consider amiodarone or sotalol.Because interest in VPC supression decreased when it was shown to be typically deleterious in patients with coronary artery disease, this literature is not current, and specifically the role of newer class III antiarrhythmic like dofetilide and azimilide for VPCs is unclear

disease.Step 3: The next step in patients who cannot take flecainide or propafenone is to consider amiodarone or sotalol.Because interest in VPC supression decreased when it was shown to be typically deleterious in patients with coronary artery disease, this literature is not current, and specifically the role of newer class III antiarrhythmic like dofetilide and azimilide for VPCs is unclear

Cumulative experience of azimilide-associated torsades de pointes ventricular tachycardia in the 19 clinical studies comprising the azimilide database. The purpose of this study was to assess the incidence, temporal characteristics, and risk factors associated with azimilide-associated torsades de pointes (TdP) ventricular tachycardia. Azimilide dihydrochloride is a class III antiarrhythmic drug possessing Ikr and Iks channel-blocking properties. Oral azimilide (75 to 125 mg/day) was taken by 5,375 patients in 19 clinical trials conducted at 775 international centers. Of 3,964 patients in double-blind studies, 1,427 had a history of atrial fibrillation or other supraventricular arrhythmia, 510 had an implantable cardioverter-defibrillator, and 2,027 were post-myocardial infarction patients

the choice of an antiarrhythmic drug for the treatment of AF. Recently approved antiarrhythmics, such as dofetilide, and promising investigational drugs, such as azimilide and dronedarone, may change the treatment landscape for AF. For medical conversion of recent-onset AF, class IC antiarrhythmic drugs, administered as an oral bolus, have been demonstrated to be the most efficacious pharmacologic

fibrillation in heart failure patients because of their neutral effect on mortality and their tolerance by patients with low ejection fractions. Although amiodarone and azimilide carry a low potential for producing torsades de pointes compared with sotalol and dofetilide, the prevalence of torsades de pointes in women is at least twice that in men for all these drugs. Careful monitoring of the QT interval

Design of the SHock Inhibition Evaluation with Azimilide (SHIELD) study: a novel method to assess antiarrhythmic drug effect in patients with an implantable cardioverter-defibrillator. This report presents the rationale and study design details of the SHock Inhibition Evaluation with Azimilide study, which is recruiting 624 patients with implantable cardioverter-defibrillators (ICDs) who are at risk for life-threatening ventricular arrhythmia, randomized to azimilide 75 mg, azimilide 125 mg, or placebo and followed for 1 year. The objective of this study is to determine the effect of azimilide versus placebo on the symptomatic ventricular arrhythmia burden using a unique statistical analysis based on the unusual temporal distribution of symptomatic ICD therapies. The primary efficacy end

effects and less extracardiac toxicity is a primary aim of current investigations. At present, pharmacologic research is actively focused on developing antiarrhythmic agents with multiple or novel ion channel effects. There are 4 agents that act by simultaneously blocking multiple ion channels that are currently under regulatory review: azimilide dihydrochloride, tedisamil, dronedarone, and vernakalant

Azimilide. Azimilide is a potassium channel antagonist that, in contrast to existing class III antiarrhythmic agents, blocks both the rapidly (I(Kr)) and slowly (I(Ks)) activating components of the delayed rectifier potassium current. In animal and clinical studies, azimilide prolonged repolarisation by increasing the action potential duration and effective refractory period. In animal models , azimilide was effective in terminating both atrial and ventricular arrhythmias. Azimilide also demonstrated antifibrillatory efficacy in a canine model of sudden cardiac death. In patients with a history of atrial fibrillation/flutter, oral azimilide controlled arrhythmias more effectively than placebo in a 6-month randomised double-blind study. At a dosage of 125 mg once daily, azimilide significantly

Dose-response relations of azimilide in the management of symptomatic, recurrent, atrial fibrillation. We evaluated the efficacy and safety of azimilide, a new class III antiarrhythmic agent that blocks both the slow and fast components of the cardiac-delayed rectifier potassium currents in 4 randomized, double-blind, placebo-controlled trials with similar protocols. The purpose of this study was to assess the relation between dose and effect. A total of 1,380 patients with a documented history of symptomatic atrial fibrillation (AF), atrial flutter, or both, were enrolled. After a 3-day loading period during which the assigned dose was given twice a day, subjects received placebo or azimilide (35, 50, 75, 100, or 125 mg once a day) for the duration of the study period. The primary end point

Azimilide, a novel oral class III antiarrhythmic for both supraventricular and ventricular arrhythmias. Azimilide is an investigational Class III antiarrhythmic that has been developed for treating both supraventricular and ventricular tachyarrhythmias. Similar to other Class III antiarrhythmics, azimilide prolongs myocardial repolarization in a dose-dependent manner by increasing the action potential duration, QT interval, and effective refractory period. The most frequent reported side effect is headache, with rare serious adverse events of early reversible neutropenia and Torsades de Pointes. In long-term follow up, the patient withdrawal rate has been low. Azimilide has very predictable pharmacokinetics, is predominantly hepatically metabolized, and has no significant drug interactions

Azimilide reduces emergency department visits and hospitalizations in patients with an implantable cardioverter-defibrillator in a placebo-controlled clinical trial. The goal of this study was to determine whether azimilide, as compared with placebo, will reduce the number of emergency department (ED) visits and hospitalizations caused by arrhythmias or cardiac events in patients with an implantable cardioverter-defibrillator (ICD). Patients with an ICD may require ED visits and hospitalizations because of arrhythmias, which trigger ICD therapies. The effect of adjunctive antiarrhythmic therapy on these outcomes is not known. A total of 633 patients with an ICD were randomized in the SHIELD (SHock Inhibition Evaluation with AzimiLiDe) trial, a blinded, placebo-controlled randomized trial

Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm. Azimilide dihydrochloride (azimilide) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias. In patients with atrial fibrillation, it has shown excellent efficacy in some previous trials and minimal efficacy in others. Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter, randomized, placebo-controlled clinical trial. Patients were admitted to a hospital and randomly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily. Patients who were in sinus rhythm spontaneously or had sinus rhythm restored

Electrical storm in patients with an implantable defibrillator: incidence, features, and preventive therapy: insights from a randomized trial. The purpose of this study was to assess the incidence, features, and clinical sequelae of 'electrical storm' (ES). This study is a prospectively designed secondary analysis of SHIELD; a randomized trial of azimilide for suppression of ventricular . Frequent VT episodes accounted for 91% of all ESs, with the remaining being VF alone or both VT plus VF. ES led to a 3.1-fold increase in arrhythmia-related hospitalization (95% CI 2.3-4.3; P<0.0001) compared with patients with isolated VT/VF, and to a 10.2-fold increase (95% CI 6.4-16.3; P<0.0001) compared with patients without VT/VF. Compared with placebo, azimilide (75 and 125 mg/day) reduced the risk

Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial. Treatment of atrial fibrillation remains a major clinical challenge owing to the limited efficacy and safety of anti-arrhythmic drugs, particularly in patients with structural heart disease. To evaluate the efficacy of azimilide, a new class III anti -arrhythmic drug, we studied 658 patients with symptomatic persistent atrial fibrillation, adequate anticoagulant therapy, and planned electrical cardioversion. Patients were randomized to placebo, azimilide (125 mg o.d.), or sotalol (160 mg b.i.d.). Primary efficacy analysis was based on event recurrence, which was defined as atrial fibrillation lasting>24 h, or requiring DC cardioversion. Median time

Efficacy of azimilide for the maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation in the presence and absence of structural heart disease. Azimilide hydrochloride (azimilide), an investigational antiarrhythmic drug, has shown variable efficacy in preventing atrial fibrillation (AF). This study was designed to assess its efficacy in maintaining sinus rhythm in patients with paroxysmal AF and heart disease. Patients with symptomatic paroxysmal AF were screened for 1 month by transtelephonic monitoring. After recording 1 episode of AF in the screening period, they were randomized to receive azimilide 125 mg or placebo once daily. Patients were stratified by the presence or absence of congestive heart failure or coronary heart disease (CHF/CHD). A maximum of 220 patients without

Influence of coadministration on the pharmacokinetics of azimilide dihydrochloride and digoxin. The influence of coadministration on digoxin and azimilide pharmacokinetics/pharmacodynamics was assessed in a randomized, 3-way crossover study in 18 healthy men. Serial blood and urine samples were obtained for azimilide and digoxin quantitation. Treatment effects on pharmacokinetics were assessed using analysis of variance. The relationship between azimilide blood concentrations and QT(c) prolongation was characterized by an E(max) model. Effects of coadministration on pharmacodynamics were assessed using a mechanistic-based inhibition model. Azimilide pharmacokinetics was unaffected by digoxin, except for a 36% increase in CL(r) (P = .0325), with no change in CL(o). Digoxin pharmacokinetics

Symptoms at the time of arrhythmia recurrence in patients receiving azimilide for control of atrial fibrillation or flutter: results from randomized trials. Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide pain, shortness of breath, dizziness, or sweating. Patients were required to answer yes or no. A symptom score was created varying from 0 to 6, in increasing order of number of symptoms reported. This was compared for patients receiving either of 2 doses of azimilide or placebo. The relationship between the number of symptoms, heart rate at time of arrhythmia recurrence and treatment was analyzed