Dofetilide versus quinidine for atrial flutter: viva la difference!?

Abstract

Dofetilide is more effective than quinidine to terminate atrial flutter in this animal model. It is also more capable of lengthening refractoriness more uniformly than quinidine. While the investigators describe local changes in refractoriness and dispersion of refractoriness and wavelength meticulously, it is not clear which, if any, of these properties cause flutter termination or influence reinduction. This report provides new insight into the electrophysiologic mechanisms of antiarrhythmic drugs used to treat atrial arrhythmias. Related investigations are needed to expand our knowledge of the actions of antiarrhythmic drugs, how these drugs affect critical portions of the reentrant circuit, and how to identify potential adverse effects of these agents. Application of these data may help guide the use of antiarrhythmic drugs and allow development of safer, and yet more potent, compounds. At least, it will give us pause about using more toxic and less effective drugs. While Class III drugs, specifically dofetilide, may be more potent and beneficial than quinidine in this model, it is uncertain that these results pertain to human reentrant atrial arrhythmias, particularly, atrial flutter. Perhaps dofetilide will be effective for certain types of atrial flutter requiring an anatomical center defined by an area of injury or surgical scar in the right atrium. The fact that these, and previous, data indicate a specific beneficial effect of dofetilide, particularly on atrial flutter, is interesting. Even if dofetilide proves highly effective for human atrial flutter, its safety will need to be proven in large clinical trials. The most obvious concern about dofetilide is development of serious side effects such as torsades de pointes. Clinical trials of this drug for atrial arrhythmias are presently ongoing. Ultimately, the long-term use of such a drug is dependent on the emergence of other highly effective therapies such as radiofrequency ablation.