56-80: Enhanced Antiarrhythmic Effects of Dofetilide in a Largely African American Population. (10th June 2016) - Mironov, Alexander
Abstract: Purpose: Dofetilide is a class III antiarrhythmic agent which prolongs myocyte repolarization by acting on the delayed rectified potassium ion channel. This occasionally results in QT interval prolongation requiring in-hospital EKG monitoring during therapy initiation. Participants included in manufacturer trials were >90% Caucasian and >70% male. The purpose of our study was to measure clinical outcomes in a more diverse patient population. Methods: This retrospective cohort study identified all patients who recently underwent initial administration of dofetilide at our institution for control of atrial or ventricular arrhythmias. Medical and demographic data was collected through chart review. We then compared the rate of dose adjustment, therapy discontinuation, and cardioversion with published data on mostly Caucasian patients. The Fisher's Exact Test was used for statistical analysis. Results: Out of 54 patients, 27 male and 27 female, 35 identified themselves as African American, 12 as Caucasian, 6 as Hispanic, and 1 as Asian. Adjustment of the initial dose, on the basis of creatinine clearance, was similar to previous studies (24% vs 23%, P 0.86). While fewer patients required dose down titration due to QTc prolongation, this was not statistically significant (14.8% vs 22.1%, P 0.37). Notably, dofetilide therapy was stopped due to QTc prolongation more frequently in our population (22.2% vs 6.5%, P 0.015). Our patients also experienced a much greater rate of cardioversion from atrial fibrillation or atrial flutter to sinus rhythm (77.7% vs 27.4%, P <0.0001) during the first 36 hours of therapy. One person experienced Torsades de Pointes. There were no statistically significant gender differences in QTc prolongation or rate of cardioversion. Conclusions: In a population consisting of mostly African American and Hispanic patients, dofetilide was much more effective at converting atrial fibrillation and atrial flutter to sinus rhythm. However, the rate of therapy discontinuation due to QTc prolongation was also increased. We believe further investigation is warranted into the etiology of these findings.