Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter.
OBJECTIVE
To discuss the clinical pharmacology of the antiarrhythmic drug ibutilide in patients with atrial fibrillation (AF) or atrial flutter (AFl).


METHODS
A MEDLINE search (January 1983-December 1997) was used to identify pertinent English-language articles on ibutilide. Key search terms included ibutilide, AF, AFl, cardioversion, and sinus rhythm. The MEDLINE search was supplemented by references included in the bibliographies of comprehensive review articles and studies.


METHODS
Studies and review articles describing the chemistry, pharmacology, and pharmacokinetics of ibutilide were selected. All abstracts and published clinical trials evaluating the efficacy and safety were reviewed.


METHODS
Pertinent information on the pharmacology and mechanism of action of ibutilide was summarized. Data were extracted from the clinical trials describing trial design, patient population, interventions, methods of evaluation, outcomes, and statistical significance.


RESULTS
Ibutilide is a Vaughan-Williams class III antiarrhythmic agent approved for intravenous use for the rapid termination of recent-onset AF or AFl. The drug is extensively metabolized by the liver, has a volume of distribution of 11-15 L/kg, is 40% protein bound, and has an elimination half-life of 6 hours (range 2-12). Data from two placebo-controlled trials demonstrated the efficacy of ibutilide for converting AF or AFl of short duration (< or = 90 d) to normal sinus rhythm. A third placebo-controlled trial demonstrated efficacy in patients who developed AF or AFl following cardiac surgery. Comparative trials with procainamide and sotalol have shown at least similar and perhaps superior efficacy with ibutilide. There are no comparative trials with other antiarrhythmic drugs or with direct current cardioversion (DCC). In 586 clinical trial patients receiving ibutilide, the most significant adverse effect was the development of torsade de pointes in 25 patients (4.3%) including 10 cases (1.7%) in which the rhythm was sustained. All cases of torsade de pointes were terminated electrically and none resulted in death or severe morbidity. No prospective cost-effectiveness studies are available; however, results from two decision models suggest that ibutilide may have advantages over other drugs and first-line electrical cardioversion.


CONCLUSIONS
Ibutilide appears to be an effective alternative method for rapid conversion of recent-onset AF or AFl. The drug may be particularly useful in patients who have undergone recent cardiac surgery or those who are not ideal candidates for DCC. Although studies suggest that the risk of proarrhythmia and in particular torsade de pointes is relatively low, caution is advised until additional experience is gained in clinical practice.
Howard
P A
PA
Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City 66160, USA. phoward@kumc.edu
D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001282:Atrial Flutter / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D016239:MEDLINE; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*