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(Circulation. 2000;101:e200.)
© 2000 American Heart Association, Inc.

Cardiovascular News

Safety and Effectiveness of Dofetilide for Conversion of Atrial Fibrillation and Nesiritide for Acute Decompensation of Heart Failure

A Report from the Cardiovascular and Renal Advisory Panel of the Food and Drug Administration

Cindy L. Grines, MD

From William Beaumont Hospital, Royal Oak, Mich.

Correspondence to Cindy L. Grines, MD, William Beaumont Hospital, Division of Cardiology, 3601 W Thirteen Mile Road, Royal Oak, MI 48073-6769. E-mail cgrines@beaumont.edu

Key Words: anti-arrhythmia agents • atrial flutter • atrial natriuretic factor • heart failure

The Cardiovascular and Renal Advisory Panel of the Food and Drug Administration (FDA) met to discuss the safety and effectiveness of the antiarrhythmic agent dofetilide and the natriuretic peptide nesiritide.

Dofetilide (Tikosyn)

Dofetilide is a class III antiarrhythmic agent that prolongs the effective refractory period by blocking a single type of potassium channel (I_kr). Data were presented from 2 large efficacy trials¹ and a mortality trial (Danish Investigation of Arrhythmia and Mortality ON Dofetilide [DIAMOND])² in support of a proposal to market an oral formulation of dofetilide for the conversion of chronic atrial fibrillation/flutter (AF) to normal sinus rhythm and for the maintenance of sinus rhythm once converted. Dofetilide was not effective in patients with paroxysmal AF or with paroxysmal supraventricular arrhythmias.

Study 345 enrolled 671 patients in Europe who had AF for <2 years. Study 120 enrolled 325 patients in North America who had a more recent onset of AF (2 weeks to 6 months). Three different doses (125 µg, 250 µg, and 500 µg) were compared with placebo. In these trials and in subsequent studies, doses were decreased if creatinine clearance was low or if the QT interval (averaged over 10 to 15 beats) was increased by >15%; after the initiation of therapy, all patients were monitored in the hospital for 3 days. In both large AF trials, dofetilide was superior to placebo at terminating AF within 3 days of therapy, especially at the 500-µg dose (30% versus 1.5%, P<0.001); however, with the addition of electrical cardioversion, restoration . . . [Full Text of this Article]