TREATMENT OF CHRONIC VENTRICULAR EXTRASYS TOLES BY PROPAFENONE (600 MG D) IN 2 OR 3 DAILY SUBDOSES/

The efficacy of propafenone by oral route in the treatment of chronic ventricular extrasystoles (VES) was investigated in 14 subjects in the context of a multicenter evaluation carried out double blind and usin g a crossover sequence. The purpose of this study was to compare the a ntiarrythmic efficacy of a dose of 600 mg/d of propafenone randomly di vided into two or three subdoses. After carrying out two Holter record ings (< 15 days) the patients presenting with chronic (less-than-or-eq ual-to 100 VES/H) and stable (interindividual variability greater-than -or-equal-to 30 %) ventricular extrasystoles were included. The treatm ent period consisted of two 8-day courses divided by a placebo period and carried out following a crossover mode. The efficacy of treatment was defined as a reduction in the VES by at least 70 % relative to the second Holter during the inclusion period which was used as the refer ence period. Fourteen patients (57.2 +/- 18.2 years) from eight cardio logical centers (eight with heart disease) were included. In general, propafenone at a dose of 600 mg/d bid or tid significantly reduced the total number of VES by about 65 % : 15239 +/- 2663 VES/24 h (baseline ) to 5238 +/- 2746 VES/24 h (bid) and 5765 +/- 2683 VES/24 h (tid) ; p < 0.0001, with no significant difference between the bid and tid trea tments. Individually, 8 patients (57 %) responded during the bid treat ment, 7 patients (50 %) during the tid treatment and 6 patients during both treatments. Of the nine patients presenting with a significant d oublet rate, the global number was reduced : 168.4 +/- 214/24 h (basel ine) to 33.9 +/- 53.8/24 h (bid) and 173 +/- 584.4/24 h (tid) but with no significant difference relative to the control period. Individuall y, in about half of the patients, the doublet rate was significantly r educed (greater-than-or-equal-to 90 % complex VES). No proarrythmic ef fect was observed. The cardiovascular side effects were moderate and i t was never necessary to discontinue propafenone. This study confirms the antiarrythmic efficacy of propafenone in the treatment of chronic VES in about two thirds of patients at a daily dose of 600 mg with sim ilar efficacy bid and tid.