ELECTROPHYSIOLOGIC EFFECTS AND ANTIARRHYTHMIC EFFICACY OF DIPRAFENONE IN PATIENTS WITH SUSTAINED VENTRICULAR-TACHYCARDIA

The electrophysiologic and antiarrhythmic effects of diprafenone, a dimethyl analog of propafenone, were investigated in 20 patients (18 men and 2 women, mean age: 61 +/-10 years) with coronary artery disease undergoing programmed stimulation because of sustained ventricular tachycardia (VT). The left ventricular ejection fraction averaged 39 +/- 11%. All patients had failed at least one class I or class III antiarrhythmic agent (mean 2,3 +/- 1,3 drugs). During baseline (drug-free) study sustained VT was induced in all patients by programmed ventricular stimulation using a maximum of 3 premature ventricular extra-stimuli. Oral diprafenone, at a mean daily dose of 380 +/- 73 mg, given for at least 4 days, significantly decreased sinus cycle length and significantly increased PR, QRS and QTc intervals. Six patients developed AV-block I (PR > 0.2 s). In 4 patients (20%), sustained VT occurred spontaneously after initiation of diprafenone therapy. In 3 out of these 4 patients, therapy was discontinued. In the remaining 17 patients diprafenone did not prevent the induction of sustained VT, although it rendered VT more difficult to induce in 7 patients. The drug resulted in a pronounced increase in VT-cycle length from 289 +/- 52 to 338 +/- 88 ms (p < 0.001). Right ventricular effective refractory period increased from 257 +/- 35 to 270 +/- 24 ms (p < 0.05). Thus, diprafenone exerts electrophysiologic effects characterized by slowing of conduction and prolongation of refractory periods. The pronounced effects of the drug on sinus cycle length and the PR interval can be attributed to its additional beta-sympatholytic action. During acute electrophysiologic testing, diprafenone is only minimally effective for preventing VT in patients with underlying coronary artery disease. Its additional beta-sympatholytic properties do not seem to offer additional benefits.