Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms.
OBJECTIVE
To assess the clinical criteria predicting the short and long-term efficacy of propafenone, an agent with class IC antiarrhythmic activity and a broad pharmacological profile.


METHODS
Prospective study of propafenone at doses of 450 to 900 mg/day during a six week dose titration period (including a placebo phase with two separate 24 Holter recordings). Responders to treatment were followed for one year.


METHODS
One hundred patients with frequent ventricular arrhythmias (greater than 30 extrasystoles/h) of Lown class III and IVA/B and without evidence of myocardial infarction within the past six months.


METHODS
Multivariate regression analysis of spontaneous arrhythmia variability and of different clinical variables to determine the short and long-term efficacy and safety of propafenone.


RESULTS
Propafenone 450 mg/day was effective in 30/100 patients (30%), and at 600 mg/day another 14 responded. The efficacy of propafenone correlated with a low spontaneous arrhythmia variability and, as shown by multivariate analysis, with a lower patient age (p less than 0.05). When the dose was increased to 900 mg/day a further six (12%) patients responded. However, with increasing doses of propafenone, the one year probability of effective treatment decreased from 86% (450 mg/day) to 67% (600 mg/day) and to 44% (900 mg/day). After restudying the patients at three, six, and 12 months and after dose adjustment in 11/44 patients (25%), 31 patients (70%) remained responders. Loss of permanent antiarrhythmic efficacy was best predicted by the initial dose that achieved a response. No patient died suddenly or had arrhythmogenic effects during Holter monitoring. Side effects occurred in 36% of patients but these rarely limited long-term treatment.


CONCLUSIONS
A younger age, low spontaneous arrhythmia variability, and particularly a low titration dose were the best predictors of the short and long term efficacy of propafenone. All other responders should have repeated Holter recordings during the first year of treatment.
Zehender
M
M
Medizinische Klinik III, Albert-Ludwigs-Universität Freiburg, Germany.
Hohnloser
S
S
Geibel
A
A
Furtwängler
A
A
Olschewski
M
M
Meinertz
T
T
Just
H
H
D000328:Adult; D000367:Age Factors; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D003327:Coronary Disease / Q000150:complications; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011405:Propafenone / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies
D011405:Propafenone