Prevention of Atrial Fibrillation After Cardioversion - Results of the PAFAC Trial.

T Fetsch (1), G Breihardt (1), R. Engberding (2), HP Koch (3), J Lukl (4), HW Müller (3), M Oeff (5), HJ Trappe (6), N Treese (7). (1) University Hospital of Münster Germany, (2) General Hospital of Wolfsburg, Germany, (3) Knoll Deutschland Ludwigshafen, Germany, (4) General Hospital of Olomouc, Czech Republic, (5) General Hospital of Brandenburg, Germany, (6) University of Bochum, Marienhospital Herne, Germany, (7) Marienhospital Osnabrück Germany.

Purpose: To answer three major questions of clinical relevance: 1. How frequent are documented recurrences of atrial fibrillation (AF) in long-term follow-up? 2. Is the frequency of AF recurrences significantly reduced by sotalol or quinidine + verapamil? 3. How safe is antiarrhythmic treatment for the prevention of AF recurrences with special respect to proarrhythmic effects in long-term follow-up?

Design: Over 39 months, 1,182 pts. presenting documented chronic AF were prospectively included in the study in 99 centres in Germany and in the Czech Republic, 848 pts. (mean age 62 years, 66% male) were successfully DC cardioverted and double-blindly randomized to either sotalol (383 pts.), quinidine + verapamil (377 pts.) or placebo (88 pts.). Endpoints were either documented AF recurrence or death of any kind. All pts. were followed until an endpoint occurred or the end of the total trial was reached. The mean FU period was 249 ± 315 days. All pts. received a personal small ECG recorder (Tele ECG) and were asked to record and transmit via telephone at least 1 ECG per day during the total follow-up, in case of symptoms as often as necessary. All ECGs were immediately analyzed in a central unit. AF recurrences documented by ECG were assumed as valid episodes, only, independent of related symptoms. In case of AF, a fax was sent immediately to the investigator, initiating an extraordinary visit with the subsequent differentiation in paroxysmal or chronic AF by Holter recordings. A total of 191,103 ECGs were recorded and transmitted, of which 96% were valid for complete analysis (88% categorized as "good" or "very good" quality).

Efficacy results: In 572 pts. (67%) at least one episode of AF recurrence was documented in FU, in 352 pts. (42%) AF was subsequently defined as chronic. The total recurrence rates (first episode of any AF) after 1 year were 88% for placebo, 73% for sotalol and 70% for quinidine + verapamil. The recurrence rates for chronic AF after 1 year were 77% for placebo, 50% for sotalol and 38% for quinidine + verapamil. About 95% of all AF recurrences were primarily detected in the daily Tele ECG. About 90% of all AF recurrences occurred completely asymptomatic.

Safety results: A total of 8 ventricular tachycardias (0.9%), 10 syncopes (1.2%), 3 ventricular fibrillations (0.4%), 1 successful resuscitation (0.1%), 9 Torsade de pointes (TdP) tachycardias (1.0%) and 11 deaths (1.3%) occurred during the active study period. The risk profiles of sotalol and quinidine + verapamil were comparable with the exception of all TdP tachycardias occurring under sotalol. All pts. were again followed after 1 year, independent of the individual end of the active study period. After the active study period, 13 additional deaths occurred (1.6%).

Conclusions: Antiarrhythmic treatment after DC cardioversion decreases recurrence rates significantly compared to placebo (2- to 3-times). The efficacy of quinidine + verapamil is superior to sotalol. Recurrence rates detected by Tele ECG are higher than expected. The risk profiles of quinidine + verapamil and sotalol are comparable with the exception of all TdP tachycardias occurring under sotalol. The additional risk of life-threatening events under antiarrhythmic therapy is ~ 3.5% to 4%. The total mortality in the active study period and after the active period were comparable. Symptoms are not reliable as clinical surrogates to detect episodes of AF (~90% of all recurrences are asymptomatic). Clinical definitions and therapeutic strategies based on symptoms have to be discussed. The results of large controlled trials in the past need re-evaluation.