title: Safety of oral dofetilide for rhythm control of atrial fibrillation and atrial flutter.
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).
  
  
  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.affiliation: 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.
authors.forename: JoEllyn M
authors.initials: JM
authors.lastname: Abraham
authors.affiliation: 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.).
authors.forename: Walid I
authors.initials: WI
authors.lastname: Saliba
authors.affiliation: 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.).
authors.forename: Carolyn
authors.initials: C
authors.lastname: Vekstein
authors.affiliation: 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.).
authors.forename: David
authors.initials: D
authors.lastname: Lawrence
authors.affiliation: 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.).
authors.forename: Mandeep
authors.initials: M
authors.lastname: Bhargava
authors.affiliation: 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.).
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bassiouny
authors.affiliation: 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.).
authors.forename: David
authors.initials: D
authors.lastname: Janiszewski
authors.affiliation: 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.).
authors.forename: Bruce
authors.initials: B
authors.lastname: Lindsay
authors.affiliation: 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.).
authors.forename: Michael
authors.initials: M
authors.lastname: Militello
authors.affiliation: 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.).
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.affiliation: 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.).
authors.forename: Stacy
authors.initials: S
authors.lastname: Poe
authors.affiliation: 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.).
authors.forename: Christine
authors.initials: C
authors.lastname: Tanaka-Esposito
authors.affiliation: 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.).
authors.forename: Kathy
authors.initials: K
authors.lastname: Wolski
authors.affiliation: 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.).
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Wilkoff
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D001282:Atrial Flutter / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D002423:Cause of Death / Q000639:trends; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D009820:Ohio / Q000453:epidemiology; D010627:Phenethylamines / Q000008:administration & dosage*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide
keywords: Torsade de pointes; anti-arrhythmic drugs; atrial fibrillation; atrial flutter; dofetilide