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Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators - Azimilide and Recurrent VT in Patients With ICDs
Description:
The goal of the trial was to evaluate the effect of azimilide dihydrochloride, a novel antiarrhythmic, on the recurrence of implantable cardioverter defibrillator (ICD) therapies (shocks and antitachycardia pacing [ATP]) in patients with documented ventricular tachycardia (VT) who had an ICD.
Hypothesis:
Treatment with azimilide dihydrochloride will be associated with a reduction in the frequency of shocks and ATP in patients with VT who had an ICD.
Study Design
Study Design:
Patients Enrolled: 172
Mean Follow Up: Mean 247-285 days
Mean Patient Age: Mean age 64-69 years
Female: 11
Mean Ejection Fraction: LVEF was <35% in 62% of patients.
Patient Populations:
Either 1) an ICD implanted ≥30 days prior to randomization, and the patient had at least one ICD shock within the preceding year; or 2) an ICD implanted for symptomatic VT within 30 days of randomization, and the patient had an inducible sustained monomorphic VT
Exclusions:
Age <18 years; class IV New York Heart Association heart failure; taking class I or class III antiarrhythmic agents; unresolved angina pectoris or had experienced a myocardial infarction within 90 days of randomization; QTc longer than 440 ms or JTc >320 ms (if QRS >120 ms); history of polymorphic VT, including torsade de pointes; hypertrophic cardiomyopathy or restrictive heart disease; hemodynamically unstable; or had clinically significant liver or renal dysfunction
Primary Endpoints:
Frequency of shocks and ATP
Drug/Procedures Used:
Patients were randomized to either 35 mg (n=44), 75 mg (n=45), or 125 mg (n=46) of oral azimilide dihydrochloride or placebo (n=37). All patients were evaluated at baseline, two weeks, and months 1, 3, 6, 9, and 12. At each follow-up visit, a physical examination with adverse event (AE) assessment, 12-lead ECG, and clinical laboratory parameters were performed.
Concomitant Medications:
All patients had an ICD.
Principal Findings:
ICD therapies (appropriate shocks and ATP) were significantly lower in patients in the azimilide arms compared with the placebo group (10, 12, and 9 incidences per patient year in the 35 mg, 75 mg, and 125 mg arms vs. 36 incidences per patient year in the placebo arm; hazard ratio [HR] 0.31 and p<0.0001 for each dose group vs. placebo). Appropriate ATP therapies were also reduced in the azimilide arms compared with the placebo group (9.1, 13.8, and 6.8 incidences per patient year in the 35 mg, 75 mg, and 125 mg arms vs. 42.1 incidences per patient year in the placebo arm; p<0.0001 for each dose group vs. placebo).
There was no increase in AEs in the azimilide arms versus placebo (mean AEs per patient 4.5, 6.2, 6.0 vs. 5.9 in the placebo arm, p=NS) or in the number of drug-related AEs (32%, 36%, 37% vs. 38% for placebo). There was no difference in change from baseline in left ventricular ejection fraction (LVEF), resting heart rate, or minimal energy requirements for defibrillation or pacing in the azimilide dihydrochloride groups versus placebo.
Interpretation:
Among patients with documented VT who had an ICD, treatment with the novel antiarrhythmic azimilide dihydrochloride was associated with a reduction in the frequency of shocks and ATP compared with placebo, without increases in adverse events. There was no dose response observed in the frequency of shocks and ATP in the azimilide groups. The larger Shock Inhibition Evaluation with Azimilide (SHIELD) trial is currently underway to confirm the findings of this pilot study.
References:
Singer I, Al-Khalidi H, Niazi I, et al. Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators. J Am Coll Cardiol 2004;43:39-43.
Keywords: Tachycardia, Ventricular, Follow-Up Studies, Imidazolidines, Stroke Volume, Piperazines, Electrocardiography, Heart Rate, Calcium Channel Blockers, Defibrillators, Implantable
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