A randomized trial of budiodarone in paroxysmal atrial fibrillation.

Abstract

OBJECTIVE:

The aim of this study was to investigate the preliminary safety and efficacy of three doses of budiodarone in patients with paroxysmal atrial fibrillation.

BACKGROUND:

Budiodarone is a chemical analogue of amiodarone and shares its mixed ion channel electrophysiological properties. It has a shorter half-life than amiodarone.

METHODS:

Patients with paroxysmal atrial fibrillation and a previously implanted dual-chamber pacemaker capable of storing electrograms for at least 4 weeks were enrolled. Pacemaker memories were used to quantify atrial tachycardia/atrial fibrillation burden (AT/AFB). All antiarrhythmic drugs were stopped for greater than five half-lives and amiodarone greater than 3 months prior to enrollment. Following a 4-week baseline period to assess AT/AFB off antiarrhythmic drugs, patients with AT/AFB between 3% and 70% were blindly randomized to placebo, 200, 400, or 600 mg BID of budiodarone for 12 weeks followed by a 4-week washout period. Pacemakers were interrogated and safety assessed every 4 weeks. Pacemaker-derived electrograms were adjudicated blinded to treatment assignment. The primary study endpoint was percent change from baseline AT/AFB over 12 weeks of treatment compared to placebo.

RESULTS:

Of 72 randomized patients, 61 completed the study. The median reduction of AT/AFB for the 400 and 600 mg BID groups vs. placebo was 54% and 74% (p = 0.01 and 0.001), respectively. The budiodarone dose-response was statistically significant (p < 0.001). Number and duration of AT/AF episodes were reduced.

CONCLUSIONS:

In this preliminary study, budiodarone at both higher doses significantly reduced AT/AFB. The study is novel because dual-chamber pacemakers, previously placed for standard clinical indications, were successfully used to monitor AT/AFB.

• Authors: Michael D Ezekowitz, Rangadham Nagarakanti, Andrzej Lubinski, Olga Bandman, Daniel Canafax, David J Ellis, Peter G Milner, Margaret Ziola, Bernard Thibault, Stefan H Hohnloser, PASCAL Investigators
• Journal: Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing (J Interv Card Electrophysiol) Vol. 34 Issue 1 Pg. 1-9 (Jun 2012) ISSN: 1572-8595 [Electronic] Netherlands
• PMID: 22205496 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Asthmatic Agents
• budiodarone
• Amiodarone

Topics

• Aged
• Aged, 80 and over
• Amiodarone (administration & dosage, analogs & derivatives)
• Anti-Asthmatic Agents (administration & dosage)
• Atrial Fibrillation (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Internationality
• Male
• Middle Aged
• Placebo Effect
• Treatment Outcome