Discontinuation of Dofetilide From QT Prolongation and VT
What is the incidence of QT prolongation or ventricular tachycardia (VT) resulting in discontinuation of dofetilide in a real-world setting?
The authors analyzed 114 consecutive patients with atrial fibrillation (AF), hospitalized to start dofetilide at the Minneapolis Veterans Affairs Health Care System from 2011-2014. Clinical, demographic, laboratory, and medication data were obtained from electronic medical records.
The mean age of the patients was 64 ± 8 years. Dofetilide was discontinued in 22 (19%) patients due to 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, 1.1-3.4; p = 0.04) compared to those who were not taking any other QT-prolonging drugs.
The authors concluded that the incidence of QT prolongation or VT leading to discontinuation of dofetilide is remarkably higher in the real-world setting than in clinical trials.
The present study suggests that the real-world discontinuation rate of dofetilide is 20%. At least one prior, much larger study of real-world practice suggested that it was closer to 12%. In large clinical trials leading to the approval of the drug, <3% of patients had to discontinue the medication. Many factors may play a role in the decision to discontinue dofetilide. They include coadministration of drugs known to prolong QT interval in general or directly interact with dofetilide elimination, provider’s confidence in the measurement of the QT interval during atrial fibrillation, and a host of intangible factors affecting risk benefit assessment, such as the severity of symptoms, eligibility for alterative antiarrhythmic medications or ablation, and the last case discussed at the mortality and morbidity conference. In light of this and other studies, it was perplexing to learn that the Food and Drug Administration recently removed the Risk Evaluation and Mitigation Strategies (REMS) restriction on prescribers and pharmacies, so that any physician or nurse practitioner may now prescribe this potentially dangerous drug, and any pharmacy may dispense it.
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