Dofetilide - A review of its use in atrial fibrillation and atrial flutter

Dofetilide is a 'pure' class III antiarrhythmic agent which has demonstrate d efficacy in the conversion of atrial fibrillation or flutter to sinus rhy thm and the maintenance of sinus rhythm. By blocking the rapid component of the cardiac delayed rectifier potassium current (I-Kr), dofetilide prolongs the cardiac action potential duration a nd the effective refractory period. This is thought to increase the likelih ood of a re-entrant wavefront encountering refractory tissue and terminatin g the arrhythmia. Preliminary findings from the EMERALD (European and Australian Multicenter Evaluative Research on Atrial Fibrillation Dofetilide) and SAFIRE-D (Sympto matic atrial Fibrillation Investigation and Randomized Evaluation of Dofeti lide) studies suggest that oral dofetilide is effective in the conversion o f atrial fibrillation or flutter to sinus rhythm, Both studies have yet to be published in full. In SAFIRE-D. dofetilide 500 mu g twice daily for 3 da ys achieved a conversion rate of 32% compared with a 1% rate for placebo, A similar conversion rate was achieved after 3 days in EMERALD with dofetili de 500 mu g twice daily (29%) which was significantly greater than that ach ieved with sotalol 80mg twice daily (6%; p < 0.05). Oral dofetilide also appears to be effective in the maintenance of sinus rh ythm. An abstract report of EMERALD participants who had been converted to sinus rhythm showed that 71% of patients who received oral dofetilide remai ned in sinus rhythm after 6 months (compared with 26% of placebo and 59% of sotalol recipients; both p < 0.05). Restoration of sinus rhythm using intravenous dofetilide is more Likely in patients with recent-onset versus prolonged-duration arrhythmia, and in tho se with atrial flutter rather than atrial fibrillation. Limitations of comp arative data for intravenous dofetilide are such that few conclusions can b e drawn, Although generally well tolerated in clinical trials, dofetilide has proarr hythmic potential, Torsade de pointes ventricular tachycardia was reported in up to 3.3% of patients who received oral dofetilide in the DIAMOND (Diam ond Investigations of Arrhythmia and Mortality on Dofetilide) studies, alth ough only a small proportion of patients in these studies had atrial fibril lation; most episodes occurred within the first 3 days, Whether the propens ity of dofetilide for this life-threatening arrhythmia is similar to that o f Ether class III antiarrhythmic agents has vet to be determined. Important ly, the long term use of oral dofetilide in patients at high risk for sudde n cardiac death is not associated with an increased risk of mortality altho ugh these DIAMOND findings cannot necessarily be extrapolated to patients w ith atrial fibrillation. Conclusions: Dofetilide offers an alternative to currently available antiar rhythmic agents for the pharmacological conversion of atrial fibrillation o r atrial flutter to sinus rhythm and for the maintenance of sinus rhythm af ter cardioversion. However, further comparative data are necessary before i ts definitive place can be determined.