Dofetilide is a 'pure' class III antiarrhythmic agent which has demonstrated efficacy in the conversion of
atrial fibrillation or flutter to sinus rhythm 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 and the effective refractory period. This is thought to increase the likelihood of a re-entrant wavefront encountering refractory tissue and terminating the
arrhythmia. Preliminary findings from the EMERALD (European and Australian Multicenter Evaluative Research on
Atrial Fibrillation Dofetilide) and SAFIRE-D (Symptomatic
Atrial Fibrillation Investigation and Randomized Evaluation of
Dofetilide) studies suggest that oral
dofetilide is effective in the conversion of
atrial fibrillation or flutter to sinus rhythm. Both studies have yet to be published in full. In SAFIRE-D,
dofetilide 500microg twice daily for 3 days 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
dofetilide 500microg twice daily (29%) which was significantly greater than that achieved with
sotalol 80mg twice daily (6%; p < 0.05). Oral
dofetilide also appears to be effective in the maintenance of sinus rhythm. An abstract report of EMERALD participants who had been converted to sinus rhythm showed that 71% of patients who received oral
dofetilide remained 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 those with
atrial flutter rather than
atrial fibrillation. Limitations of comparative data for intravenous
dofetilide are such that few conclusions can be drawn. Although generally well tolerated in clinical trials,
dofetilide has proarrhythmic potential.
Torsade de pointes ventricular tachycardia was reported in up to 3.3% of patients who received oral
dofetilide in the
DIAMOND (
Diamond Investigations of
Arrhythmia and Mortality on
Dofetilide) studies, although only a small proportion of patients in these studies had
atrial fibrillation; most episodes occurred within the first 3 days. Whether the propensity of
dofetilide for this life-threatening
arrhythmia is similar to that of other class III antiarrhythmic agents has yet to be determined. Importantly, the long term use of oral
dofetilide in patients at high risk for
sudden cardiac death is not associated with an increased risk of mortality, although these
DIAMOND findings cannot necessarily be extrapolated to patients with
atrial fibrillation.
CONCLUSIONS: