Cp. Lau et al., Control of paroxysmal atrial fibrillation recurrence using combined administration of propafenone and quinidine, AM J CARD, 86(12), 2000, pp. 1327-1332
Citations number
25
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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 quini
dine 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 symptomati
cally controlled. The 19 refractory patients were randomized in a double-bl
inded 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/da
y, each for an 8-week study period, and subsequently crossed over to the al
ternative treatment, The resulting serum propafenone concentrations were 25
9 +/- 208 and 336 +/- 237 mg/day (p >0.5), respectively, Both treatment arm
s prolonged the time to the first symptomatic atrial fibrillation (AF) recu
rrence and the interval between attacks, and AF was controlled in 37% of pa
tients. However, the higher dose of propafenone was associated with gastroi
ntestinal side effects not present with the low-dose quinidine combination.
Of the 10 refractory patients, 7 were further controlled with a standard d
ose 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 necess
itating withdrawal were observed in 6%, and uncontrolled AF in 5% of patien
ts, There was no difference in the mean AF rate during recurrences in all p
hases, and ventricular proarrhythmia was not seen. This study documents the
role of stepwise antiarrhythmic treatment of PAF, The use of a standard do
se of propafenone, followed by low-dose quinidine combination to reduce pro
pafenone degradation, and the combined standard dose of propafenone and qui
nidine may be used to maximize efficacy and tolerability, (C) 2000 by Excer
pta Medica, Inc.