JoEllyn M Abraham1, Walid I Saliba2, Carolyn Vekstein2, David Lawrence2, Mandeep Bhargava2, Mohamed Bassiouny2, David Janiszewski2, Bruce Lindsay2, Michael Militello2, Steven E Nissen2, Stacy Poe2, Christine Tanaka-Esposito2, Kathy Wolski2, Bruce L Wilkoff2. 1. From the Minneapolis Heart Institute, MN (J.M.A.); Department of Cardiovascular Medicine, Cleveland Clinic, OH (W.I.S., M. Bhargava, M. Bassiouny, D.J., B.L., M.M., S.E.N., S.P., C.T.-E., K.W., B.L.W.); Brown University, Providence, RI (C.V.); and Department of Internal Medicine, Johns Hopkins Hospital, Baltimore, MD (D.L.). JoEllyn.Abraham@allina.com. 2. From the Minneapolis Heart Institute, MN (J.M.A.); Department of Cardiovascular Medicine, Cleveland Clinic, OH (W.I.S., M. Bhargava, M. Bassiouny, D.J., B.L., M.M., S.E.N., S.P., C.T.-E., K.W., B.L.W.); Brown University, Providence, RI (C.V.); and Department of Internal Medicine, Johns Hopkins Hospital, Baltimore, MD (D.L.).
Abstract
BACKGROUND: Although dofetilide is 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 dofetilide for 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. Dofetilide loading 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 dofetilide compared 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: Dofetilide loading 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 dofetilide and in those patients who experienced TdP while loading.
BACKGROUND: Although dofetilide is 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 dofetilide for 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. Dofetilide loading 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 dofetilide compared 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:Dofetilide loading 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 dofetilide and in those patients who experienced TdP while loading.
Authors: Jae Hyung Cho; So Jin Youn; JoEllyn C Moore; Roxanne Kyriakakis; Carolyn Vekstein; Michael Militello; Stacy M Poe; Kathy Wolski; Patrick J Tchou; Niraj Varma; Mark J Niebauer; Mandeep Bhargava; Walid I Saliba; Oussama M Wazni; Bruce D Lindsay; Bruce L Wilkoff; Mina K Chung Journal: Circ Arrhythm Electrophysiol Date: 2017-10
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