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European Heart Journal 2000 21(15):1265-1273; doi:10.1053/euhj.1999.2039
Copyright © 2000 by the European Society of Cardiology.
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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

L Bianconia,f1, A Castroa, M Dinellib, P Albonib, A Pappalardoc, E Richiardid and M Santinia

a Division of Cardiology, San Filippo Neri Hospital, Rome, Italy
b Division of Cardiology, Santissima Annunziata Hospital, Cento, Italy
c Cardiology Service—ICU, Policlinico Casilino, Rome, Italy
d Division of Cardiology, General Hospital, Asti, Italy

revised December 6, 1999; accepted December 18, 1999

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.

Key Words: dofetilide, amiodarone, antiarrhythmic drugs, atrial fibrillation, atrial flutter, cardioversion

f1 Correspondence: Dr Leopoldo Bianconi, Via San Sotero 12, 00165 Rome, Italy. Email:kofler@opbg.net

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[Abstract]
  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[Web of Science][Medline]
  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[CrossRef][Web of Science][Medline]
  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[CrossRef][Web of Science][Medline]
  5. Donovan KD, Power BM, Hockings BEF, Dobb GJ, Lee K-Y. Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation. Am J Cardiol. 4-1-1995;75:693–697
  6. Madrid AH, Moro C, Marín-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[Abstract/Free Full Text]
  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[Abstract]
  8. Vita JA, Friedman PL, Cantillon C, Antman EM. Efficacy of intravenous propafenone for the acute management of atrial fibrillation. Am J Cardiol. 5-15-1989;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[CrossRef][Web of Science][Medline]
  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[Abstract/Free Full Text]
  11. Vandenbosch R, Lisin N, Andriange M, Gach J, Carlier J. Clinical experimentation with intravenously administered disopyramide. Acta Cardiol. 1975;30:267–278[Web of Science][Medline]
  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[Web of Science][Medline]
  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[Abstract/Free Full Text]
  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[Abstract]
  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[Abstract/Free Full Text]
  16. Katritsis D, Camm AJ. New class III antiarrhythmic drugs. Eur Heart J. 1993;14:93–99[Abstract]
  17. Eur Heart J. 1991;12:1112–1131[Abstract/Free Full Text]
  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[Abstract/Free Full Text]
  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[Abstract]
  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[CrossRef][Web of Science][Medline]
  22. Sedgwick ML, Lip G, Rae AP, Cobbe SM. Chemical cardioversion of atrial fibrillation with intravenous dofetilide. Int J Cardiol. 1995;49:159–166[CrossRef][Web of Science][Medline]
  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[CrossRef][Web of Science][Medline]
  24. Olshansky B, Wilber DJ, Hariman RJ. Atrial flutter—update on the mechanism and treatment. Pacing Clin Electrophysiol. 1992;15:2308–2335[CrossRef][Medline]
  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[Abstract/Free Full Text]
  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[Web of Science][Medline]
  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[CrossRef][Web of Science][Medline]
  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[Abstract/Free Full Text]
  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[Web of Science][Medline]
  30. Kowey PR, VanderLugt JT, Luderer JR. Safety and risk/benefit analysis of ibutilide for acute conversion of atrial fibrillation/flutter. Am J Cardiol. 10-17-1996;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

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