A preliminary assessment of the effects of ATI-2042 in subjects with paroxysmal atrial fibrillation using implanted pacemaker methodology.
OBJECTIVE
ATI-2042 (budiodarone) is a chemical analogue of amiodarone with a half life of 7 h. It is electrophysiologically similar to amiodarone, but may not have metabolic and interaction side effects. The sophisticated electrocardiograph logs of advanced DDDRP pacemakers were used to monitor the efficacy of ATI-2042. The aim of this study was to determine the preliminary efficacy and safety of ATI-2042 in patients with paroxsymal atrial fibrillation (PAF) and pacemakers.


RESULTS
Six women with AF burden (AFB) between 1 and 50% underwent six sequential 2-week study periods. Patients received 200 mg bid of ATI-2042 during Period 2 (p2), 400 mg bid during p3, 600 mg bid during p4, 800 mg bid during p5, and no drug during baseline and washout (p1 and p6). Pacemaker data for the primary outcome measure AFB were downloaded during each period. Mean AFB decreased between baseline and all doses: AFB at baseline (SD) was 20.3 +/- 14.6% and mean AFB at 200 mg bid was 5.2 +/- 4.2%, at 400 mg bid 5.2 +/- 5.2%, at 600 mg bid 2.8 +/- 3.4%, and at 800 mg bid 1.5 +/- 0.5%. The mean reductions in AFB at all doses of ATI-2042 were statistically significant (P < 0.005). Atrial fibrillation burden increased in washout. Atrial fibrillation episodes tended to increase with ATI-2042, but this was offset by substantial decreases in episode duration. ATI-2042 was generally well tolerated.


CONCLUSIONS
ATI-2042 effectively reduced AFB over all doses studied by reducing mean episode duration. A large-scale study will be required to confirm this effect.
Arya
Anita
A
Eastbourne District General Hospital, King's Drive, Eastbourne BN21 2UD, UK. anitaarya@doctors.org.uk
Silberbauer
John
J
Teichman
Sam L
SL
Milner
Peter
P
Sulke
Neil
N
Camm
A John
AJ
D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000031:analogs & derivatives*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D001572:Benzofurans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008875:Middle Aged; D010138:Pacemaker, Artificial; D011446:Prospective Studies; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D001572:Benzofurans; C499879:celivarone; D000638:Amiodarone