title: Dofetilide reduces the frequency of ventricular arrhythmias and implantable cardioverter defibrillator therapies.
abstract: BACKGROUND
  Patients with an implanted cardioverter defibrillator (ICD) and ventricular arrhythmias leading to ICD therapies have poor clinical outcomes and quality of life. Antiarrhythmic agents and catheter ablation are needed to control these arrhythmias. Dofetilide has only been approved for the treatment of atrial fibrillation. The role of dofetilide in the control of ventricular arrhythmias in patients with an ICD has not been established.
  
  
  OBJECTIVE
  Evaluate the safety and efficacy of dofetilide in a consecutive group of patients with an ICD and recurrent ventricular tachycardia (VT) and/ or ventricular fibrillation (VF) after other antiarrhythmic drugs have failed to suppress these arrhythmias.
  
  
  METHODS
  We studied 30 patients (age 59 ± 11; 5 women) with symptomatic VT or VF and ICDs for secondary prevention of sudden cardiac death. These patients had an average of 1.8 ± 4.5 episodes of VT/VF per month despite antiarrhymic therapy. Twenty-one patients (70%) had recurrent appropriate ICD therapies prior to initiation of dofetilide, and 9 (30%) VTs below the programmed detection rate of the ICD. Twenty-three patients (77%) had coronary artery disease. Mean ejection fraction was 30 ± 14% and 26/30 (87%) had congestive heart failure. All patients had previously failed 2 ± 1 antiarrhythmic drugs including amiodarone (n = 19) and sotalol (n = 10).
  
  
  RESULTS
  During the first month of treatment, 25 patients (83%) had complete suppression of VT/VF and of the 21 patients with ICD therapies 16 (76%) had no therapies during the first month of treatment. During a follow-up period of 32 ± 32 months, dofetilide reduced the monthly episodes of VT/VF from 1.8 ± 4.5 to 1.0 ± 3.5 (P = 0.006). Monthly ICD therapies decreased from 0.9 ± 1.4 to 0.4 ± 1.7 (P = 0.037). In 9 patients that presented with slow VTs under the ICD detection zone, dofetilide reduced monthly VT/VF episodes from 0.7 ± 0.6 to 0.1 ± 0.1 (P = 0.01) and 6 (67%) had no further ICD therapies. Dofetilide was discontinued in 13 patients (43%) after 24 ± 30 months due to failure to control VT/VF (n = 7), placement of a left ventricular assist device (n = 3), catheter ablation (n = 1), heart transplantation (n = 1), and left ventricular restoration surgery (n = 1). There were 7 documented deaths (2 patients died suddenly; 3 patients of progressive heart failure; and 2 of non-cardiac causes).
  
  
  CONCLUSIONS
  In patients with an ICD and ventricular arrhythmias, dofetilide decreases the frequency of VT/VF and ICD therapies even when other antiarrhythmic agents, including amiodarone, have previously been ineffective. Recurrences still occur in some patients requiring catheter ablation, mechanical support, or heart transplantation.
authors.affiliation: Heart & Vascular Institute, Penn State College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Giselle A
authors.initials: GA
authors.lastname: Baquero
authors.forename: Javier E
authors.initials: JE
authors.lastname: Banchs
authors.forename: Sondra
authors.initials: S
authors.lastname: Depalma
authors.forename: Sallie K
authors.initials: SK
authors.lastname: Young
authors.forename: Erica D
authors.initials: ED
authors.lastname: Penny-Peterson
authors.forename: Soraya M
authors.initials: SM
authors.lastname: Samii
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Wolbrette
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Naccarelli
authors.forename: Mario D
authors.initials: MD
authors.lastname: Gonzalez
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000150:complications; D003324:Coronary Artery Disease / Q000150:complications; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D017147:Defibrillators, Implantable; D004305:Dose-Response Relationship, Drug; D004554:Electric Countershock; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide