Safety of oral dofetilide for rhythm control of atrial fibrillation and atrial flutter.

Background— Although dofetilideis widely used in the United States for rhythm control of atrial fibrillation, there is limited postapproval safety data in the atrial fibrillation population despite its known risk of Torsade de pointes(TdP). Methods and Results— We conducted a retrospective chart review of a cohort of 1404 patients initially loaded on dofetilidefor atrial fibrillation suppression at the Cleveland Clinic from 2008 to 2012 to evaluate the incidence and risk factors for in-hospital adverse events and the long-term safety of continued use. Of the 17 patients with TdP during loading (1.2%), 10 had a cardiac arrest requiring resuscitation (1 death), 5 had syncope/ presyncope, and 2 were asymptomatic. Dofetilideloading was stopped for 105 patients (7.5%) because of QTc prolongation or TdP. Variables correlated with TdP were (1) female sex, 2) 500-μg dose, (3) reduced ejection fraction, and (4) increase in QTc from baseline. One-year all-cause mortality was higher in patients who continued dofetilidecompared with those who discontinued use (hazard ratio, 2.48; 95% confidence interval, 1.08–5.71; P =0.03). Those patients who had a TdP event had higher one-year all-cause mortality than those who did not (17.6% versus 3% at 1 year; P <0.001). Conclusions— Dofetilideloading has a low but finite risk of TdP and other adverse events that warrant the current Food and Drug Administration–mandated practice of inpatient monitoring during drug loading. In this cohort, all-cause mortality was higher at 1 year in those patients continued on dofetilideand in those patients who experienced TdP while loading.