Discontinuation of Dofetilide From QT Prolongation and Ventricular Tachycardia in the Real World

Abstract

Objectives: The purpose of this study was to determine the incidence and correlates of QT prolongation or ventricular tachycardia (VT) resulting in discontinuation of dofetilide in a real-world setting.

Background: Dofetilide is a class III antiarrhythmic agent approved for achieving and maintaining sinus rhythm in patients with symptomatic atrial fibrillation. Because of a risk of QT prolongation and VT, patients starting dofetilide need to be hospitalized for 3 days to closely monitor telemetry and electrocardiography. In large clinical trials, <3% of patients had to discontinue dofetilide because of QT prolongation, but data from real-world experience are lacking.

Methods: We examined 114 consecutive patients with atrial fibrillation who were hospitalized for starting dofetilide at the Minneapolis Veterans Affairs Health Care System from 2011 to 2014.

Results: The mean age of the patients was 64 ± 8 years. Dofetilide was discontinued in 22 (19%) patients because of QT prolongation (17%) or VT (2%). A total of 32 (28%) patients were taking other QT-prolonging drugs. Of these, 10 (31%) had to discontinue dofetilide versus 12 (15%) of the 82 patients who were not taking any other QT-prolonging drugs (p = 0.04). Patients who were taking concomitant QT-prolonging drugs were 1.9 times more likely to discontinue dofetilide (95% confidence interval: 1.1 to 3.4; p = 0.04) compared with those who were not taking any other QT-prolonging drugs.

Conclusions: The incidence of QT prolongation or VT that lead to discontinuation of dofetilide is remarkably higher in the real-world setting than in clinical trials. Concomitant use of other QT-prolonging drugs was associated with discontinuation of dofetilide.

Keywords: QT prolongation; atrial fibrillation; dofetilide.