Symptoms at the time of arrhythmia recurrence in patients receiving azimilide for control of atrial fibrillation or flutter: results from randomized trials.
BACKGROUND
Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence


METHODS
At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating. Patients were required to answer yes or no. A symptom score was created varying from 0 to 6, in increasing order of number of symptoms reported. This was compared for patients receiving either of 2 doses of azimilide or placebo. The relationship between the number of symptoms, heart rate at time of arrhythmia recurrence and treatment was analyzed.


RESULTS
In 2 separate studies, azimilide at a dose of 125 mg/day significantly reduced the number of symptoms at the time of arrhythmia recurrence compared to placebo. On the other hand, in 2 studies, the dose of 100 mg/day did not significantly reduce symptom burden. The individual symptoms significantly reduced by azimilide125 mg/day were fatigue, shortness of breath, chest pain and dizziness. Palpitations and sweating were not significantly reduced. Modeling of heart rate at the time of arrhythmia recurrence, symptoms and treatment indicated that a small reduction in heart rate with azimilide accounted for only a small part of the symptom reduction. There was another effect of azimilide: an average reduction of 0.38 symptoms (P <.01) that was independent of heart rate.


CONCLUSIONS
Azimilide (125 mg/day) reduces the number of symptoms reported at the time of AF recurrence.
Connolly
Stuart J
SJ
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Schnell
Daniel J
DJ
Page
Richard L
RL
Wilkinson
William E
WE
Marcello
Stephen R
SR
Pritchett
Edward L C
EL
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D001282:Atrial Flutter / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D002637:Chest Pain / Q000517:prevention & control; D004244:Dizziness / Q000517:prevention & control; D004311:Double-Blind Method; D004417:Dyspnea / Q000517:prevention & control; D005221:Fatigue / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006827:Hydantoins; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D048289:Imidazolidines; D010879:Piperazines / Q000008:administration & dosage* / Q000494:pharmacology; D012008:Recurrence
D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; C086123:azimilide