Therapeutic effectiveness and plasma levels of single or combination use of class I antiarrhythmic agents for ventricular arrhythmias

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 (p less than 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 (greater than or equal to 150 beats/min) showed a significant effect while only 4 of the 12 patients with non-fast VT rate (greater than or equal to 100 and 150 beats/min) had a significant one (p less than 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 microgram/ml, 1.08 +/- 0.41 microgram/ml, 0.85 +/- 0.43 microgram/ml and 268.2 +/- 123.3 ng/ml, respectively.