Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azimilide, a novel class III antiarrhythmic agent, blocks both the slowly activating (IKs) and rapidly activating (IKr) components of the delayed rectifier potassium current, which distinguishes it from conventional potassium channel blockers such as sotalol and dofetilide, which block only IKr. Azimilide is being developed to prolong the time to recurrence of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia in patients with and without structural heart disease. Azimilide is also being studied for its role in prevention of sudden cardiac death in high-risk patients after myocardial infarction (MI). Preclinical and clinical studies indicate that azimilide prolongs cardiac refractory period in a dose-dependent manner, as manifested by increases in action potential duration, QTc interval, and effective refractory period. Azimilide does not affect PR or QRS interval and minimally affects hemodynamic properties such as blood pressure and heart rate. Its in vivo effects appear to be rate-independent and are maintained under ischemic or hypoxic conditions, properties of potential clinical significance. Azimilide has shown excellent efficacy (>85%) in suppressing supraventricular arrhythmias in a variety of dog models. It also suppressed complex ventricular arrhythmias in infarcted dogs and, in a sudden death cardiac model, decreased mortality. Azimilide pharmacokinetics are very predictable. The drug is completely absorbed, and the extent of absorption is not affected by food. It can be administered once daily. Clinical data suggest that dose adjustments of azimilide are not required for age, gender, hepatic or renal function, or concomitant use of digoxin or warfarin. Azimilide has a good safety profile in open-label safety studies in >800 supraventricular arrhythmia patients, most with structural heart disease. The incidence of serious adverse events, including torsade de pointes, is low. The rate of patient withdrawal from long-term studies is also encouragingly low. Unlike amiodarone, azimilide has shown no evidence of pulmonary or ocular toxicity. Azimilide is expected to provide a unique new therapy for the prevention of supraventricular arrhythmias and sudden cardiac death when Phase III clinical trials are complete and safety and efficacy are confirmed.
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PMID:Azimilide dihydrochloride, a novel antiarrhythmic agent. 953 22

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 with digoxin or warfarin. In animal models, azimilide has been shown to be very effective in suppressing both atrial and ventricular tachyarrhythmias, decreasing the defibrillation energy requirement, and preventing post-myocardial infarction ventricular tachycardia and fibrillation. Clinically, in a series of 4 double-blind, randomized, placebo-controlled trials, the Azimilide Supraventricular Arrhythmia Program which included over 1000 patients and approximately 70% with structural heart disease, azimilide showed a significant prolongation in the time to first recurrence of paroxysmal supraventricular tachycardia or atrial fibrillation/flutter. With respect to ventricular tachyarrhythmias, the AzimiLide post-Infarct surVival Evaluation Trial was a large randomized, multinational, prospective, placebo-controlled study in recent survivors of myocardial infarction at high risk for sudden cardiac death. After 1 year of follow-up, this study showed no statistical difference in all-cause mortality between placebo and azimilide. However, azimilide did statistically reduce the incidence of new atrial fibrillation. Further trials are necessary to evaluate the efficacy of azimilide in patients with symptomatic ventricular arrhythmias.
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PMID:Azimilide, a novel oral class III antiarrhythmic for both supraventricular and ventricular arrhythmias. 1572 Feb 25

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 CHF/CHD were randomized, with the remainder having CHF/CHD. Patients with CHF/CHD were monitored for 3 days during loading. The primary efficacy analysis was the time to the first symptomatic recurrence of AF in the CHF/CHD group. Secondary analyses were the time to the first recurrence in the entire population and the time to the first recurrence in those with significant structural heart disease. The median time to recurrence of AF in the CHF/CHD group was 10 days in the 2 treatment arms. Nonsignificant trends were seen toward efficacy of azimilide in the CHF/CHD group (hazard ratio 1.28, 95% confidence interval 0.97 to 1.70, p=0.087), structural heart disease group (hazard ratio 1.22, 95% confidence interval 0.96 to 1.56, p=0.11), and overall group (hazard ratio 1.22, 95% confidence interval 1.00 to 1.49, p=0.053). No patient died. In conclusion, azimilide showed a nonsignificant trend toward efficacy in maintaining sinus rhythm in patients with AF.
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PMID:Efficacy of azimilide for the maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation in the presence and absence of structural heart disease. 1682 95