Safety of a controlled-release flecainide acetate formulation in the prevention of paroxysmal atrial fibrillation in outpatients.
OBJECTIVE
The cardiac safety of a once-a-day 200 mg controlled-release formulation of flecainide acetate in the prevention of paroxysmal atrial fibrillation (PAF) was assessed in outpatients.


METHODS
The drug was administered for 24 weeks to 227 patients diagnosed with recurrent Paf episodes. Cardiac safety was assessed primarily by the maximum change from baseline in QRS duration. Changes in left ventricular function at echocardiography, incidence of proarrhythmic effects determined from ECG and Holter recordings and cardiovascular adverse events were also taken into account to assess cardiac safety. Efficacy was documented by actuarial methods.


RESULTS
Mean maximum QRS increase from baseline was 11.4% (n = 181); QRS increase was < 15% in 71.8% of the patients and > or = 25% in 18.8%. Only 4 patients had maximum QRS value > 100 ms under treatment. Left ventricular ejection fraction remained within +/- 20% of baseline for 90% of the patients, increased above 20% for 8.6% and decrease below 30% for 1.4% (n = 139). Bradycardia (13.2%; n = 129) and ventricular extrasystoles (10.6%; n = 104) were the most frequently identified proarrhythmic effects. Atrio-ventricular block (4.0%), supra-ventricular tachycardia (2.2%), bundle branch block (1.8%) and atrial fibrillation (1.3%) were the most frequent drug-related cardiac adverse events. Estimated treatment success rate was 74% (95% CI: [68%; 80%]) and the incidence of Paf episodes decreased from baseline 28.6% to 11.0% (P < 0.0001).


CONCLUSIONS
We provided evidence for a good cardiac safety profile of the controlled-release formulation of flecainide acetate and confirmed the effectiveness of the drug in the prevention of PAF recurrences.
Aliot
E
E
Service de cardiologie, centre hospitalier universitaire, hôpital Central, rue du Morvan, 54500 Nancy, France.
De Roy
L
L
Capucci
A
A
Hernández
J
J
Denjoy
I
I
Lupoglazoff
J M
JM
Coumel
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000517:prevention & control*; D001919:Bradycardia / Q000188:drug therapy; D003692:Delayed-Action Preparations / Q000494:pharmacology / Q000627:therapeutic use; D004562:Electrocardiography; D005260:Female; D005424:Flecainide / Q000494:pharmacology / Q000627:therapeutic use*; D006327:Heart Block / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance / Q000706:statistics & numerical data; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D018879:Ventricular Premature Complexes / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D003692:Delayed-Action Preparations; D005424:Flecainide