The frequent recurrence of
paroxysmal atrial fibrillation (PAF) despite the use of standard antiarrhythmic agents prompted the use of new therapeutic approaches. There are few data on systematic assessment of PAF control with stepwise dose escalation and the use of a
drug combination. Low-dose
quinidine may promote the efficacy of
propafenone by inhibiting its degradation through the
cytochrome P450 pathway (
CYP2D6). We prescribed
propafenone 300 to 450 mg/day to 60 patients with PAF for 8 weeks, and 62% were symptomatically controlled. The 19 refractory patients were randomized in a double-blinded fashion to receive either a higher dose of
propafenone (450 to 675 mg/day) or the standard dose of
propafenone with low-dose
quinidine 150 mg/day, each for an 8-week study period, and subsequently crossed over to the alternative treatment. The resulting serum
propafenone concentrations were 259 +/- 208 and 336 +/- 237 mg/day (p >0.5), respectively. Both treatment arms prolonged the time to the first symptomatic
atrial fibrillation (AF) recurrence and the interval between attacks, and AF was controlled in 37% of patients. However, the higher dose of
propafenone was associated with gastrointestinal side effects not present with the low-dose
quinidine combination. Of the 10 refractory patients, 7 were further controlled with a standard dose of
propafenone plus
quinidine (600 mg/day). Overall, control of PAF was achieved in 85% of patients at the end of 8 months; adverse effects necessitating withdrawal were observed in 6%, and uncontrolled AF in 5% of patients. There was no difference in the mean AF rate during recurrences in all phases, and ventricular proarrhythmia was not seen. This study documents the role of stepwise antiarrhythmic treatment of PAF. The use of a standard dose of
propafenone, followed by low-dose
quinidine combination to reduce
propafenone degradation, and the combined standard dose of
propafenone and
quinidine may be used to maximize efficacy and tolerability.