Dofetilide for the treatment of premature ventricular complexes and ventricular tachycardia in patients with structural heart disease

J Cardiovasc Electrophysiol. 2024 Dec;35(12):2363-2371. doi: 10.1111/jce.16452. Epub 2024 Oct 3.

Abstract

Background: Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it has been used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardias (VTs).

Objective: The purpose of this study was to determine the efficacy and safety of dofetilide for ventricular arrythmias (VAs).

Methods: In this retrospective cohort study, 81 patients (59 men; age = 60 ± 14 years; LVEF = 0.34 ± 0.16) were admitted for dofetilide initiation to treat PVCs (29), VTs (42) or both (10). A ≥ 80% decrease in PVC burden was defined as a satisfactory response. An ICD was present in 72 patients (89%). Another antiarrhythmic was previously used in 50 patients (62%). Prior catheter ablation had been performed in 33 patients (41%).

Results: During intitiation, dofetilide was discontinued in 12 patients (15%) due to QT prolongation (8) and inefficacy to suppress VAs (4). Among the 32 patients with PVCs who successfully started dofetilide, the mean PVC burden decreased from 20 ± 10% to 8 ± 8% at a median follow-up of 2.6 months (p < .001). PVC burden was reduced by ≥80% in only 11/32 patients (34%). During 7 ± 1 years of follow-up, 41/69 patients (59%) continued to have VAs and received appropriate ICD therapies for monomorphic VTs (35) and polymorphic VT/VF (6) at a median of 8.0 (IQR 2.6-33.2) months. Dofetilide had to be discontinued in 50/69 patients (72%) due to inefficacy or intolerance. The composite outcome of VT/VF recurrence, heart transplantation, or death occurred in 6/12 patients (50%) without dofetilide and 49/69 patients (71%) with dofetilide. The event free survival was similar between patients treated with and without dofetilide (log-rank p = .55).

Conclusions: Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress the occurrence of VTs in a majority of patients.

Keywords: antiarrhythmic drug; dofetilide; premature ventricular complex; ventricular Tachycardia; ventricular arrhythmia.

MeSH terms

  • Action Potentials / drug effects
  • Aged
  • Anti-Arrhythmia Agents* / adverse effects
  • Anti-Arrhythmia Agents* / therapeutic use
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Phenethylamines* / adverse effects
  • Phenethylamines* / therapeutic use
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Sulfonamides* / adverse effects
  • Sulfonamides* / therapeutic use
  • Tachycardia, Ventricular* / diagnosis
  • Tachycardia, Ventricular* / drug therapy
  • Tachycardia, Ventricular* / physiopathology
  • Time Factors
  • Treatment Outcome
  • Ventricular Premature Complexes* / diagnosis
  • Ventricular Premature Complexes* / drug therapy
  • Ventricular Premature Complexes* / physiopathology

Substances

  • Phenethylamines
  • dofetilide
  • Anti-Arrhythmia Agents
  • Sulfonamides

Grants and funding