What is the role of dofetilide in treating ventricular tachycardia?

Dofetilide for Ventricular Tachycardia

Dofetilide is not recommended as a first-line agent for ventricular tachycardia and should only be considered after failure of other antiarrhythmic medications in patients with recurrent ventricular tachycardia who are not candidates for catheter ablation. While dofetilide has demonstrated some efficacy in treating ventricular tachycardia, its use carries significant risks, particularly torsade de pointes, requiring careful patient selection and monitoring.

Efficacy in Ventricular Tachycardia

• Dofetilide is a Class III antiarrhythmic agent that works by blocking the rapid component of the delayed rectifier potassium current (IKr), which prolongs the cardiac action potential duration and effective refractory period 1
• In patients with ventricular tachycardia and ICDs who had failed other antiarrhythmic drugs (including amiodarone), dofetilide reduced the frequency of VT/VF episodes from 1.8 ± 4.5 to 1.0 ± 3.5 per month (p=0.006) 2
• In a comparative study with sotalol in patients with ischemic heart disease and inducible sustained VT, dofetilide showed similar efficacy (35.9% vs 33.6% response rate) 3

Placement in Treatment Algorithm

1. First-line options:

   • Catheter ablation (preferred for recurrent VT)
   • Amiodarone
   • Sotalol (particularly in patients with ischemic heart disease)

2. Second-line options:

   • Dofetilide (only after failure of first-line agents)
   • Other antiarrhythmic medications

3. Considerations for dofetilide use:

   • Patients with structural heart disease or ischemic heart disease who have failed other therapies
   • Patients who are not candidates for catheter ablation
   • Patients who have failed amiodarone or sotalol therapy

Safety Concerns and Monitoring Requirements

• Risk of torsade de pointes: Dofetilide can cause serious ventricular arrhythmias, primarily torsade de pointes, which is directly related to plasma concentration 1
• Mandatory hospitalization: Treatment must be initiated in a facility with continuous ECG monitoring for a minimum of 3 days 1
• Renal function assessment: Creatinine clearance must be calculated before administration of the first dose, as dofetilide is primarily eliminated by the kidneys 1
• QT interval monitoring: Regular ECG monitoring is required to assess for QT prolongation 1
• Drug interactions: Multiple medications can increase dofetilide plasma levels by inhibiting renal tubular secretion or CYP3A4 metabolism 1

Dosing Considerations

• Dosing is based on creatinine clearance to reduce the risk of proarrhythmia 1
• For patients with normal renal function, the typical dose is 500 μg twice daily 1
• Dose reduction is required for patients with impaired renal function:
  • CrCl 40-60 mL/min: 250 μg twice daily
  • CrCl 20-40 mL/min: 125 μg twice daily
  • CrCl <20 mL/min: Contraindicated 1

Clinical Evidence Summary

• In the DIAMOND studies, dofetilide was found to be safe in patients with left ventricular dysfunction and post-myocardial infarction 4
• A study of 30 patients with ICDs and recurrent VT/VF showed that 83% had complete suppression of VT/VF during the first month of dofetilide treatment 2
• However, during long-term follow-up (32 ± 32 months), dofetilide was discontinued in 43% of patients, with 7 patients discontinuing due to failure to control VT/VF 2

Pitfalls and Caveats

• Dofetilide is primarily approved for atrial fibrillation and atrial flutter, not ventricular tachycardia 4
• The risk of torsade de pointes is higher in women, patients with bradycardia, hypokalemia, hypomagnesemia, and renal dysfunction 5
• Dofetilide has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance 1
• Unlike sotalol, dofetilide does not have beta-blocking properties, which may be advantageous in certain patients 6
• Careful attention must be paid to concomitant medications that might increase dofetilide levels and risk of proarrhythmia 1

In conclusion, while dofetilide has shown some efficacy in treating ventricular tachycardia, its use should be limited to patients who have failed other antiarrhythmic medications and are not candidates for catheter ablation. The significant risk of torsade de pointes requires careful patient selection, mandatory hospitalization for initiation, and ongoing monitoring.