Efficacy and safety of dofetilide in patients with atrial fibrillation and atrial flutter
- 306 Downloads
Dofetilide, an IKr blocker has been demonstrated to be effective in terminating persistent atrial fibrillation and flutter (AF/AFL), and in maintaining sinus rhythm after direct current cardioversion (CV). It is not known, however, whether pharmacological conversion with dofetilide predicts maintenance of sinus rhythm. In addition, there is limited information comparing the efficacy of dofetilide in persistent versus paroxysmal AF/AFL.
Methods and Results
Eighty consecutive patients with AF/AFL (51 persistent, 29 paroxysmal) admitted for initiation of dofetilide were studied. Termination of persistent AF/AFL occurred in 61% of patients while 39% required CV. After 21 ± 19 months of follow-up, 37% of patients with persistent AF/AFL were free of recurrence. Acute conversion with dofetilide did not predict long term efficacy. Dofetilide was more effective in maintaining sinus rhythm in patients with AFL (65%) than in those with AF (25%) (p < 0.05). Dofetilide was more likely to maintain sinus rhythm in patients with persistent than paroxysmal AF/AFL (37 vs. 14%; p < 0.05). Torsades de Pointes developed in two patients despite careful dosing and monitoring of QT changes.
Dofetilide is more effective in patients with persistent than in those with paroxysmal AF/AFL. Importantly, short-term response does not necessarily predict long-term efficacy. Significant proarrhythmia can occur even with careful in-hospital monitoring.
KeywordsAtrial fibrillation Dofetilide Antiarrhythmic drugs
- 1.Fuster, V., Ryden, L. E., Cannom, D. S., et al. (2006). ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). Circulation, 114, e257–e354.PubMedCrossRefGoogle Scholar
- 5.Greenbaum, R. A. (1999). Meeting highlights: highlights of the 71st Scientific Sessions of the American Heart Association. The EMERALD trial. Circulation, 99, 2486–2491.Google Scholar
- 6.Singh, S., Zoble, R. G., Yellen, L., et al. (2000). Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on defetilide (SAFIRE-D) study. Circulation, 102, 2385–2390.PubMedGoogle Scholar
- 7.Torp-Pedersen, C., Moller, M., Bloch-Thomsen, P. E., et al. (1999). Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. The New England Journal of Medicine, 341, 857–865.PubMedCrossRefGoogle Scholar
- 9.Pedersen, O. D., Bagger, H., Keller, N., & Marchant, B. (2001). kober l, Torp-Pedersen C. Efficacy of dofetilide in the treatment of atrial fibrillation–flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy. Circulation, 104, 292–296.PubMedGoogle Scholar
- 15.Falk, R. H., Pollak, A., Singh, S. N., et al. (1997). Intravenous dofetilide a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators. Journal of the American College of Cardiology, 29(2), 385–390.PubMedCrossRefGoogle Scholar
- 18.Knobloch, K., Brendel, J., Peukert, S., et al. (2002). Electrophysiological and antiarrhythmic effects of the novel Ikur channel blockers, S9947 and S20951, on left vs. right pig atrium in vivo in comparison with the IKr blockers dofetilide, azimilide, d,l-sotalol and ibutilide. Naunyn-Schmiedeberg’s Archives of Pharmacology, 366, 482–487.PubMedCrossRefGoogle Scholar