Combination antiarrhythmic treatment among class Ia, Ib, and II agents for ventricular arrhythmias

Summary

Ventricular arrhythmia suppression trials were performed to compare the efficacies and side effects of disopyramide and mexiletine used alone and in combination, and to compare the efficacies and side effects of mexiletine and propranolol used alone and in combination, in patients with chronic ventricular premature contractions (VPCs, ≥3000 beats/day). The study on the combination of disopyramide and mexiletine included 26 patients (19 men and 7 women). Disopyramide 100 mg tid or mexiletine 150 mg tid was administered as single-drug therapy, and disopyramide 50 mg plus mexiletine 100 mg tid was administered as combination therapy. Each patient underwent Holter monitoring during four different periods: baseline, disopyramide alone, mexiletine alone, and combination therapy. The mean number of VPCs/hr at baseline was 796±522 (mean±SD), which was significantly decreased with all three therapies (p<0.01 in each) to a) 415±480 with disopyramide alone, b) 341±368 with mexiletine alone, and c) 345±408 with the combination therapy. The number of patients demonstrating a significant reduction in VPCs (≥75%) and the elimination of ventricular tachycardia (VT; three or more consecutive VPCs) did not differ significantly among the three therapies. The prematurity index (PI), vulnerability index (VI), and QTc tended to be aggravated by disopyramide therapy alone, but these values were corrected by combination therapy. No patients withdrew from the study due to side effects during combination therapy, although three patients withdrew from the study due to severe side effects during single-drug therapy. The study on the combination of mexiletine and propranolol included 19 patients (8 men and 11 women) with chronic VPCs. Mexiletine 150 mg tid or propranolol 20 mg tid was administered as single-drug therapy, and mexiletine 100 mg plus propranolol 10 mg tid was administered as combination therapy. Each patient underwent Holter monitoring during four different periods: baseline, mexiletine alone, propranolol alone, and combination therapy. The mean number of VPCs/hr was 677±572, at baseline, which was significantly reduced to a) 345±500 with mexiletine alone, b) 457±544 with propranolol alone, and c) 342±513 with combination therapy (p< 0.01 in each). The number of patients showing a significant reduction (≥75%) and the elimination of VTs did not differ among the three therapies. No patients withdrew from the study due to side effects during combination therapy, although two patients withdrew due to severe side effects during single-drug therapy. This study suggests that combination therapy with small doses of antiarrhythmic drugs is not likely to change the prematurity index, vulnerability index, or QTC. Further studies are required before these data can be extrapolated to higher doses of drugs and to patients with serious arrhythmias.