DOI: 10.1161/CIRCEP.114.002339
Safety of Oral Dofetilide for Rhythm Control of Atrial Fibrillation and Atrial Flutter
Running title: Abraham et al.; Safety of Dofetilide for Atrial Fibrillation
JoEllyn M. Abraham, MD1; Walid I. Saliba, MD2; Carolyn Vekstein, BS3; David Lawrence, MD4; Mandeep Bhargava, MD2; Mohamed Bassiouny, MD2; David Janiszewski, CNP2; Bruce Lindsay, MD2; Michael Militello, PharmD2; Steven E. Nissen, MD2; Stacy Poe, CN CNP NP2; Christine Tanaka-Esposito, MD2; Kathy Wolski, MPH2; Bruce L. Wilkoff, MD2
1
Minneapoli Minneapolis liss Heart li Hearrt In Hear Inst Institute, stiitut st itut utee, Minneapolis, Minnneeap Mi eapoliis,, MN; MN N; 2De Department epart rttment off Ca Cardiovascular ard rdio ovaasc scularr M Medicine, ediccin ed inee, e, 3 4 Clleveland Clin nicc, Cleveland, Clev eveland, ev d, OH; Br Brown row wn Un Unive University, erssity y, Providence, Prov Pr ovidden ov ncee, RI; Depa Department D epa part r mennt ooff In Internal nternnal Cleveland Clinic, Medicine, M edici cine ci ne,, Jo ne John Johns hnss Ho Hopk Hopkins pkin pk inss Ho in Hosp Hospital, sppit i al al,, Ba Balt Baltimore, ltim lt im mor ore, e, M MD D
Correspondence: C orrespondence: JoEllyn M. Abraham, MD Minneapolis Heart Institute Abbott Northwestern Hospital, part of Allina Health 920 East 28th St., Suite 300 Minneapolis, MN 55407 Tel: (612) 863-3900 Fax: (612) 863-3784 E-mail: [email protected]
Journal Subject Codes: [118] Cardiovascular pharmacology, [5] Arrhythmias, clinical electrophysiology, drugs
1 Downloaded from http://circep.ahajournals.org/ at Charité - Universitaetsmedizin Berlin on July 2, 2015
DOI: 10.1161/CIRCEP.114.002339
Abstract: Background - Although dofetilide is widely used in the United States for rhythm control of atrial fibrillation (AF), there is limited post-approval safety data in the AF population despite its known risk of Torsade de pointes (TdP). Methods and Results - We conducted a retrospective chart review of a cohort of 1,404 patients initially loaded on dofetilide for AF suppression at the Cleveland Clinic from 2008-2012 to evaluate the incidence and risk factors for in-hospital adverse events as well as the long-term safety of continued use. Of the 17 patients with TdP during loading (1.2%), 10 had a cardiac arrest requiring resuscitation (one death), 5 had syncope/pre-syncope and 2 were asymptomatic. Dofetilide loading was stopped for 105 patients (7.5%) due to QTc prolongation or TdP. Variables correlated with TdP were 1)) female ggender,, 2)) 500 mcgg dose,, 3)) reduced ejection j higher fraction, and 4) increase in QTc from baseline. One-yearr aall-cause ll-cause mortality wass hi high gher gh er iin n patients who continued dofetilide compared to those who discontinued use (HR 2.48, 2.448, 8 95%CI TdP one-year 1.08 08 to to 5.71, 5 71 5. 71,, p=0.03). p=0 03). Those patients who had a T p=0. dP P event had higher hig ighe ig h r on one e-year all-cause a mortality who year, m orrtality than tthose hose w hos hoo ddid id nnot ot ((17.6% ot 17.6 17 6% vs. 3% % att one one ye earr, pp
Safety of Oral Dofetilide for Rhythm Control of Atrial Fibrillation and Atrial Flutter
Running title: Abraham et al.; Safety of Dofetilide for Atrial Fibrillation
JoEllyn M. Abraham, MD1; Walid I. Saliba, MD2; Carolyn Vekstein, BS3; David Lawrence, MD4; Mandeep Bhargava, MD2; Mohamed Bassiouny, MD2; David Janiszewski, CNP2; Bruce Lindsay, MD2; Michael Militello, PharmD2; Steven E. Nissen, MD2; Stacy Poe, CN CNP NP2; Christine Tanaka-Esposito, MD2; Kathy Wolski, MPH2; Bruce L. Wilkoff, MD2
1
Minneapoli Minneapolis liss Heart li Hearrt In Hear Inst Institute, stiitut st itut utee, Minneapolis, Minnneeap Mi eapoliis,, MN; MN N; 2De Department epart rttment off Ca Cardiovascular ard rdio ovaasc scularr M Medicine, ediccin ed inee, e, 3 4 Clleveland Clin nicc, Cleveland, Clev eveland, ev d, OH; Br Brown row wn Un Unive University, erssity y, Providence, Prov Pr ovidden ov ncee, RI; Depa Department D epa part r mennt ooff In Internal nternnal Cleveland Clinic, Medicine, M edici cine ci ne,, Jo ne John Johns hnss Ho Hopk Hopkins pkin pk inss Ho in Hosp Hospital, sppit i al al,, Ba Balt Baltimore, ltim lt im mor ore, e, M MD D
Correspondence: C orrespondence: JoEllyn M. Abraham, MD Minneapolis Heart Institute Abbott Northwestern Hospital, part of Allina Health 920 East 28th St., Suite 300 Minneapolis, MN 55407 Tel: (612) 863-3900 Fax: (612) 863-3784 E-mail: [email protected]
Journal Subject Codes: [118] Cardiovascular pharmacology, [5] Arrhythmias, clinical electrophysiology, drugs
1 Downloaded from http://circep.ahajournals.org/ at Charité - Universitaetsmedizin Berlin on July 2, 2015
DOI: 10.1161/CIRCEP.114.002339
Abstract: Background - Although dofetilide is widely used in the United States for rhythm control of atrial fibrillation (AF), there is limited post-approval safety data in the AF population despite its known risk of Torsade de pointes (TdP). Methods and Results - We conducted a retrospective chart review of a cohort of 1,404 patients initially loaded on dofetilide for AF suppression at the Cleveland Clinic from 2008-2012 to evaluate the incidence and risk factors for in-hospital adverse events as well as the long-term safety of continued use. Of the 17 patients with TdP during loading (1.2%), 10 had a cardiac arrest requiring resuscitation (one death), 5 had syncope/pre-syncope and 2 were asymptomatic. Dofetilide loading was stopped for 105 patients (7.5%) due to QTc prolongation or TdP. Variables correlated with TdP were 1)) female ggender,, 2)) 500 mcgg dose,, 3)) reduced ejection j higher fraction, and 4) increase in QTc from baseline. One-yearr aall-cause ll-cause mortality wass hi high gher gh er iin n patients who continued dofetilide compared to those who discontinued use (HR 2.48, 2.448, 8 95%CI TdP one-year 1.08 08 to to 5.71, 5 71 5. 71,, p=0.03). p=0 03). Those patients who had a T p=0. dP P event had higher hig ighe ig h r on one e-year all-cause a mortality who year, m orrtality than tthose hose w hos hoo ddid id nnot ot ((17.6% ot 17.6 17 6% vs. 3% % att one one ye earr, pp
