Safety of dofetilide in stable patients and investigating traits of susceptibility to torsade de pointes

Background

Atrial fibrillation is the most prevalent cardiac arrhythmia, presenting symptomatic patients with diminished quality of life and worsening of heart failure. Dofetilide, a class 3 antiarrhythmic agent, is a proven and safe rhythm control medication. Initial risk of QT prolongation leading to torsade de pointes (TdP) necessitates a standard protocol mandating hospitalization for three days for initiation.

Objectives

To assess safety when adhering to initiation protocol and identify traits for susceptibility to TdP in elective dofetilide admissions.

Methods

We conducted a retrospective study involving patients admitted to Mayo Clinic sites across four states for elective inpatient initiation of dofetilide between 2003 and 2022. Patients’ charts underwent review, focusing on dofetilide-related TdP occurrences, baseline characteristics including QT intervals, laboratory values, comorbidities, and concomitant medications. Patients who experienced TdP were subjected to further evaluation to identify potential risk factors.

Results

Of 2036 patients identified, mean age 66.4 ± 11.4 years, and 67.2 % male, 16 experienced dofetilide-related TdP (incidence rate 0.79%). Notably, 81% (13/16) of TdP cases occurred in patients who deviated from the FDA/manufacturer algorithm protocol. The concomitant use of active intravenous diuretic therapy, digoxin, and QT-prolonging drugs emerged as identifiable risk factors. Additionally, females exhibited a higher incidence of TdP (1.5%) than males (0.44%) {odd ratio [OR] 3.46; P = 0.017}.

Conclusion

Overall incidence of TdP related to dofetilide initiation was low (0.79%). Adherence to protocol during elective hospital admissions appears extraordinarily safe. Patients who did not require concurrent use of intravenous diuretics, digoxin, or QT prolonging drugs exhibited lower risk of TdP.