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Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study

Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of... Abstract Aims This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm. Methods and Results One hundred and fifty patients with atrial fibrillation or flutter (duration range 2h–6 months) were given 15-min intravenous infusions of 8μg.kg−1of dofetilide (n=48), 5mg.kg−1of amiodarone (n=50), or placebo (n=52) and monitored continuously for 3h. Sinus rhythm was restored in 35%, 4%, and 4% of patients, respectively (P<0·001, dofetilide vs placebo;P=ns, amiodarone versus placebo). Dofetilide was more effective in atrial flutter than in atrial fibrillation (cardioversion rates 75% and 22%, respectively;P=0·004). The mean time to conversion with dofetilide was 55±15min. Dofetilide prolonged the QTc interval (+16% at 20min). Amiodarone substantially decreased the ventricular rate in non-converters (−18beats.min−1at 30min). Two patients given dofetilide (4%) had non-sustained ventricular tachycardias, and four (8%) had torsade de pointes, in one case requiring electrical cardioversion. Conclusion Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter. However, when infused intravenously at this dose and rate, dofetilide causes a significant incidence of torsade de pointes. dofetilide, amiodarone, antiarrhythmic drugs, atrial fibrillation, atrial flutter, cardioversion f1 " Correspondence: Dr Leopoldo Bianconi, Via San Sotero 12, 00165 Rome, Italy. Email:[email protected] References 1 Bianconi L , Mennuni M, Lukic V, Castro A, Chieffi M, Santini M. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. J Am Coll Cardiol . 1996 ; 28 : 700 –706 2 Van Gelder IC , Crijns HJ, Van Gilst WH, Verwer R, Lie KI. Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter. Am J Cardiol . 1991 ; 68 : 41 –46 3 Bellandi F , Dabizzi RP, Cantini F, Di Natale M, Niccoli L. Intravenous propafenone: efficacy and safety in the conversion to sinus rhythm of recent onset atrial fibrillation—a single-blind placebo-controlled study. Cardiovasc Drugs Ther . 1996 ; 10 : 153 –157 4 Bianconi L , Boccadamo R, Pappalardo A, Gentili C, Pistolese M. Effectiveness of intravenous propafenone for conversion of atrial fibrillation and flutter of recent onset. Am J Cardiol . 1989 ; 64 : 335 –338 5 Donovan KD , Power BM, Hockings BEF, Dobb GJ, Lee K-Y. Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation. Am J Cardiol . 1995 ; 75 : 693 –697 6 Madrid AH , Moro C, Marı́n-Huerta E, Mestre JL, Novo L, Costa A. Comparison of flecainide and procainamide in cardioversion of atrial fibrillation. Eur Heart J . 1993 ; 14 : 1127 –1131 7 Suttorp MJ , Kingma JH, Jessurun ER, Lie-A-Huen L, van Hemel NM, Lie KI. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. J Am Coll Cardiol . 1990 ; 16 : 1722 –1727 8 Vita JA , Friedman PL, Cantillon C, Antman EM. Efficacy of intravenous propafenone for the acute management of atrial fibrillation. Am J Cardiol . 1989 ; 63 : 1275 –1278 9 Fenster PE , Comess KA, Marsh R, Katzenberg C, Hager WD. Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide infusion. Am Heart J . 1983 ; 106 : 501 –504 10 Halpern SW , Ellrodt G, Singh BN, Mandel WJ. Efficacy of intravenous procainamide infusion in converting atrial fibrillation to sinus rhythm. Relation to left atrial size. Br Heart J . 1980 ; 44 : 589 –595 11 Vandenbosch R , Lisin N, Andriange M, Gach J, Carlier J. Clinical experimentation with intravenously administered disopyramide. Acta Cardiol . 1975 ; 30 : 267 –278 12 Gavaghan TP , Feneley MP, Campbell TJ, Morgan JJ. Atrial tachyarrhythmias after cardiac surgery: results of disopyramide therapy. Aust N Z J Med . 1985 ; 15 : 27 –32 13 Faniel R , Schoenfeld Ph. Efficacy of i.v. amiodarone in converting rapid atrial fibrillation and flutter to sinus rhythm in intensive care patients. Eur Heart J . 1983 ; 4 : 180 –185 14 Galve E , Rius T, Ballester R. Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study. J Am Coll Cardiol . 1996 ; 27 : 1079 –1082 15 Hou Z-Y , Chang M-S, Chen C-Y. Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone. A randomized, digoxin-controlled study. Eur Heart J . 1995 ; 16 : 521 –528 16 Katritsis D , Camm AJ. New class III antiarrhythmic drugs. Eur Heart J . 1993 ; 14 : 93 –99 17 Eur Heart J . 1991 ; 12 : 1112 –1131 18 SAS Institute, Inc., Cary, NC. SAS/STAT User's Guide. 1989. p. 1–1042 19 Crijns HJGM , Van Gelder IC, Kingma JH, Dunselman PHJM, Gosselink ATM, Lie KI. Atrial flutter can be terminated by a class III antiarrhythmic drug but not by a class IC drug. Eur Heart J . 1994 ; 15 : 1403 –1408 20 Falk RH , Pollak A, Singh SN, Friedrich T. Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. J Am Coll Cardiol . 1997 ; 29 : 385 –390 21 Frost L , Mortensen PE, Tingleff J, Platou ES, Christiansen EH, Christiansen N. Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery. Int J Cardiol . 1997 ; 58 : 135 –140 22 Sedgwick ML , Lip G, Rae AP, Cobbe SM. Chemical cardioversion of atrial fibrillation with intravenous dofetilide. Int J Cardiol . 1995 ; 49 : 159 –166 23 Suttorp MJ , Polak PE, van 't Hof A, Rasmussen HS, Dunselman PH, Kingma JH. Efficacy and safety of a new selective class III antiarrhythmic agent dofetilide in paroxysmal atrial fibrillation or atrial flutter. Am J Cardiol . 1992 ; 69 : 417 –419 24 Olshansky B , Wilber DJ, Hariman RJ. Atrial flutter—update on the mechanism and treatment. Pacing Clin Electrophysiol . 1992 ; 15 : 2308 –2335 25 Stambler BS , Wood MA, Ellenbogen KA, Perry KT, Wakefield LK, VanderLugt JT. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Circulation . 1996 ; 94 : 1613 –1621 26 Tham TCK , MacLennan BA, Burke MT, Harron DWG. Pharmacodynamics and pharmacokinetics of the class III antiarrhythmic agent dofetilide (UK-68,798) in humans. J Cardiovasc Pharmacol . 1993 ; 21 : 507 –512 27 Ikeda N , Nademanee K, Kannan R, Singh BN. Electrophysiologic effects of amiodarone: experimental and clinical observation relative to serum and tissue drug concentrations. Am Heart J . 1984 ; 108 : 890 –898 28 Wellens HJJ , Brugada P, Abdollah H, Dassen WR. A comparison of the electrophysiologic effects of intravenous and oral amiodarone in the same patient. Circulation . 1984 ; 69 : 120 –124 29 Yabek SM , Kato R, Singh BN. Effects of amiodarone and its metabolite, desethylamiodarone, on the electrophysiologic properties of isolated cardiac muscle. J Cardiovasc Pharmacol . 1986 ; 8 : 197 –207 30 Kowey PR , VanderLugt JT, Luderer JR. Safety and risk/benefit analysis of ibutilide for acute conversion of atrial fibrillation/flutter. Am J Cardiol . 1996 ; 78 : 46 –52 31 Abi Mansour P , Carberry PA, McCowan RJ, Henthorn RW, Dunn JH, Perry KT. Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial flutter and atrial fibrillation. Am Heart J . 1988 ; 136 : 632 –642 This content is only available as a PDF. The European Society of Cardiology http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study

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Publisher
Oxford University Press
Copyright
The European Society of Cardiology
ISSN
0195-668X
eISSN
1522-9645
DOI
10.1053/euhj.1999.2039
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Abstract

Abstract Aims This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm. Methods and Results One hundred and fifty patients with atrial fibrillation or flutter (duration range 2h–6 months) were given 15-min intravenous infusions of 8μg.kg−1of dofetilide (n=48), 5mg.kg−1of amiodarone (n=50), or placebo (n=52) and monitored continuously for 3h. Sinus rhythm was restored in 35%, 4%, and 4% of patients, respectively (P<0·001, dofetilide vs placebo;P=ns, amiodarone versus placebo). Dofetilide was more effective in atrial flutter than in atrial fibrillation (cardioversion rates 75% and 22%, respectively;P=0·004). The mean time to conversion with dofetilide was 55±15min. Dofetilide prolonged the QTc interval (+16% at 20min). Amiodarone substantially decreased the ventricular rate in non-converters (−18beats.min−1at 30min). Two patients given dofetilide (4%) had non-sustained ventricular tachycardias, and four (8%) had torsade de pointes, in one case requiring electrical cardioversion. Conclusion Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter. However, when infused intravenously at this dose and rate, dofetilide causes a significant incidence of torsade de pointes. dofetilide, amiodarone, antiarrhythmic drugs, atrial fibrillation, atrial flutter, cardioversion f1 " Correspondence: Dr Leopoldo Bianconi, Via San Sotero 12, 00165 Rome, Italy. Email:[email protected] References 1 Bianconi L , Mennuni M, Lukic V, Castro A, Chieffi M, Santini M. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. J Am Coll Cardiol . 1996 ; 28 : 700 –706 2 Van Gelder IC , Crijns HJ, Van Gilst WH, Verwer R, Lie KI. Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter. Am J Cardiol . 1991 ; 68 : 41 –46 3 Bellandi F , Dabizzi RP, Cantini F, Di Natale M, Niccoli L. Intravenous propafenone: efficacy and safety in the conversion to sinus rhythm of recent onset atrial fibrillation—a single-blind placebo-controlled study. Cardiovasc Drugs Ther . 1996 ; 10 : 153 –157 4 Bianconi L , Boccadamo R, Pappalardo A, Gentili C, Pistolese M. Effectiveness of intravenous propafenone for conversion of atrial fibrillation and flutter of recent onset. Am J Cardiol . 1989 ; 64 : 335 –338 5 Donovan KD , Power BM, Hockings BEF, Dobb GJ, Lee K-Y. Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation. Am J Cardiol . 1995 ; 75 : 693 –697 6 Madrid AH , Moro C, Marı́n-Huerta E, Mestre JL, Novo L, Costa A. Comparison of flecainide and procainamide in cardioversion of atrial fibrillation. Eur Heart J . 1993 ; 14 : 1127 –1131 7 Suttorp MJ , Kingma JH, Jessurun ER, Lie-A-Huen L, van Hemel NM, Lie KI. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. J Am Coll Cardiol . 1990 ; 16 : 1722 –1727 8 Vita JA , Friedman PL, Cantillon C, Antman EM. Efficacy of intravenous propafenone for the acute management of atrial fibrillation. Am J Cardiol . 1989 ; 63 : 1275 –1278 9 Fenster PE , Comess KA, Marsh R, Katzenberg C, Hager WD. Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide infusion. Am Heart J . 1983 ; 106 : 501 –504 10 Halpern SW , Ellrodt G, Singh BN, Mandel WJ. Efficacy of intravenous procainamide infusion in converting atrial fibrillation to sinus rhythm. Relation to left atrial size. Br Heart J . 1980 ; 44 : 589 –595 11 Vandenbosch R , Lisin N, Andriange M, Gach J, Carlier J. Clinical experimentation with intravenously administered disopyramide. Acta Cardiol . 1975 ; 30 : 267 –278 12 Gavaghan TP , Feneley MP, Campbell TJ, Morgan JJ. Atrial tachyarrhythmias after cardiac surgery: results of disopyramide therapy. Aust N Z J Med . 1985 ; 15 : 27 –32 13 Faniel R , Schoenfeld Ph. Efficacy of i.v. amiodarone in converting rapid atrial fibrillation and flutter to sinus rhythm in intensive care patients. Eur Heart J . 1983 ; 4 : 180 –185 14 Galve E , Rius T, Ballester R. Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study. J Am Coll Cardiol . 1996 ; 27 : 1079 –1082 15 Hou Z-Y , Chang M-S, Chen C-Y. Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone. A randomized, digoxin-controlled study. Eur Heart J . 1995 ; 16 : 521 –528 16 Katritsis D , Camm AJ. New class III antiarrhythmic drugs. Eur Heart J . 1993 ; 14 : 93 –99 17 Eur Heart J . 1991 ; 12 : 1112 –1131 18 SAS Institute, Inc., Cary, NC. SAS/STAT User's Guide. 1989. p. 1–1042 19 Crijns HJGM , Van Gelder IC, Kingma JH, Dunselman PHJM, Gosselink ATM, Lie KI. Atrial flutter can be terminated by a class III antiarrhythmic drug but not by a class IC drug. Eur Heart J . 1994 ; 15 : 1403 –1408 20 Falk RH , Pollak A, Singh SN, Friedrich T. Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. J Am Coll Cardiol . 1997 ; 29 : 385 –390 21 Frost L , Mortensen PE, Tingleff J, Platou ES, Christiansen EH, Christiansen N. Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery. Int J Cardiol . 1997 ; 58 : 135 –140 22 Sedgwick ML , Lip G, Rae AP, Cobbe SM. Chemical cardioversion of atrial fibrillation with intravenous dofetilide. Int J Cardiol . 1995 ; 49 : 159 –166 23 Suttorp MJ , Polak PE, van 't Hof A, Rasmussen HS, Dunselman PH, Kingma JH. Efficacy and safety of a new selective class III antiarrhythmic agent dofetilide in paroxysmal atrial fibrillation or atrial flutter. Am J Cardiol . 1992 ; 69 : 417 –419 24 Olshansky B , Wilber DJ, Hariman RJ. Atrial flutter—update on the mechanism and treatment. Pacing Clin Electrophysiol . 1992 ; 15 : 2308 –2335 25 Stambler BS , Wood MA, Ellenbogen KA, Perry KT, Wakefield LK, VanderLugt JT. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Circulation . 1996 ; 94 : 1613 –1621 26 Tham TCK , MacLennan BA, Burke MT, Harron DWG. Pharmacodynamics and pharmacokinetics of the class III antiarrhythmic agent dofetilide (UK-68,798) in humans. J Cardiovasc Pharmacol . 1993 ; 21 : 507 –512 27 Ikeda N , Nademanee K, Kannan R, Singh BN. Electrophysiologic effects of amiodarone: experimental and clinical observation relative to serum and tissue drug concentrations. Am Heart J . 1984 ; 108 : 890 –898 28 Wellens HJJ , Brugada P, Abdollah H, Dassen WR. A comparison of the electrophysiologic effects of intravenous and oral amiodarone in the same patient. Circulation . 1984 ; 69 : 120 –124 29 Yabek SM , Kato R, Singh BN. Effects of amiodarone and its metabolite, desethylamiodarone, on the electrophysiologic properties of isolated cardiac muscle. J Cardiovasc Pharmacol . 1986 ; 8 : 197 –207 30 Kowey PR , VanderLugt JT, Luderer JR. Safety and risk/benefit analysis of ibutilide for acute conversion of atrial fibrillation/flutter. Am J Cardiol . 1996 ; 78 : 46 –52 31 Abi Mansour P , Carberry PA, McCowan RJ, Henthorn RW, Dunn JH, Perry KT. Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial flutter and atrial fibrillation. Am Heart J . 1988 ; 136 : 632 –642 This content is only available as a PDF. The European Society of Cardiology

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European Heart Journal – Oxford University Press

Published: Aug 1, 2000

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