Mexiletine and propafenone: a comparative study of monotherapy, low, and full dose combination therapy

The electrophysiological effects of combination therapy of mexiletine and propafenone were assessed using standard 12-lead electrocardiogram (standard ECG), signal-averaged ECG (SAECG), and ambulatory ECG in 31 patients with ventricular arrhythmias. All patients underwent mexiletine monotherapy (M-mono), propafenone monotherapy (P-mono), low dose combination therapy (low M+P), and full dose combination therapy (full M+P). Full M+P increased the PQ interval and QRS duration to the same extent as P-mono did. Low M+P increased PQ interval and QRS duration to a lesser extent than P-mono and full M+P did. P-mono and full M+P significantly decreased root mean square (RMS) and increased f-QRS in SAECG, while M-mono and low M+P showed only a weak trend. SAECGs with late potentials increased in number with treatments; 9 in predrug control, 11 on M-mono, 15 on P-mono, 10 on low M+P, and 14 on full M+P. The percent suppression of frequent premature ventricular contractions (PVCs) (> 1,000/day) with M-mono, P-mono, low M+P, and full M+P were 46.4 +/- 9.0, 56.6 +/- 10.4, 64.4 +/- 9.2, and 71.4 +/- 7.1, respectively, and those of frequent couplets (> 10/day) were 58.3 +/- 17.7, 62.6 +/- 23.6, 87.5 +/- 6.2, and 92.1 +/- 4.0, respectively. Thus, full dose combination of mexiletine and propafenone exhibited the maximum antiarrhythmic efficacy without enhancement of effects on standard ECG and SAECG. Low dose combination therapy showed better antiarrhythmic efficacy in association with lesser effects on standard ECG and SAECG compared with propafenone monotherapy.