Therapeutic Effectiveness and Plasma Levels of Single or Combination Use of Class I Antiarrhythmic Agents for Ventricular Arrhythmias : SYMPOSIUM ON HIGH RISK ARRHYTHMIA ITS MECHANISM AND TREATMENT : 51th Annual Scientific Session of the Japanese Circulation Society

抄録

The efficacy of disopyramide (DP), mexiletine (MX), aprindine (AP) and cibenzoline (CZ) on ventricular arrhythmias was compared (single drug therapy). In addition, the efficacy of the combination therapy of DP with MX was also studied (combination therapy). One hundred of the 106 patients completed the protocol of the single drug therapy. Fifty percent or more reduction in the frequency of ventricular premature contractions (VPCs) was obtained in 24 of 43 patients (56%) with DP, in 24 of 44 (55%) with MX, in 18 of 29 (62%) with AP and 10 of 18 (56%) with CZ. AP was comparatively more effective than the other drugs tested. DP was significantly effective on VPCs with organic heart disease as compared to idiopathic VPCs with organic heart disease as compared to idiopathic VPCs (p < 0.05), while the other 3 drugs did not have such a tendency. With MX therapy, 10 of the 12 patients with fast VT rate (&ges; 150 beats/min) showed a significant effect while only 4 of the 12 patients with non-fast VT rate (&ges; 100 and 150 beats/min) had a significant one (p < 0.05). On the other hand, DP, AP and CZ showed almost the same efficacy at any cycle length of VT. Six patients withdrew from the study, 4 because of digestive troubles with MX therapy, 1 because of micturition disturbances with DP and 1 because of skin rash with AP. The average therapeutic plasma levels of DP, MX AP and CZ were 1.76 0.54 g/ml, 1.08 0.43 g/ml and 268.2 123.3 ng/ml, respectively. Consequently, compared to western patients, as indicated by the liberature, Japanese Patients needed only the half of the dosage and two thirds of the plasma levels to achieve almost the same efficacy. The combination therapy of DP (50 mg t.i.d.) with MX (100 mg t.i.d.), which was administered in 20 patients during hospitalization, showed approximately the same efficacy as DP (100 mg t.i.d.) or MX (150 mg t.i.d.) therapy alone, while the incidence of side effects in the combination was lower than that in DP or MX therapy alone. That is, the incidence was only 1 of the 20 patients (5%) with the combination of DP with MX, compared to 4 of 18 (22% with MX alone and 2 of 16 (13%) with DP alone. Therefore, it may be expected that combined therapy can reduce the degree of side effects with its lower dosage than the conventional dosage of each drug while retaining the same degree of efficacy as single drug therapy.