Effect of the combination of low‐dose mexiletine and metoprolol on ventricular arrhythmia

Antiarrhythmic drug therapy is often ineffective or poorly tolerated. Combining antiarrhythmic agents with different electrophysiologic properties may have a synergistic antiarrhythmic effect when compared with each drug alone. If a lower dose of each drug can be used, combination therapy may also result in lower incidence of side effects. The goal of our study was to assess the complementary effect of low-dose mexiletine and metoprolol, when compared with either drug alone. Ten patients with frequent ventricular arrhythmias including 7 patients with nonsustained ventricular tachycardia were evaluated in an open-label sequential study. The response to drug therapy was evaluated by 24-h continuous EKG monitoring, exercise stress testing, and echocardiogram after each treatment. Combination therapy effectively reduced ventricular arrhythmias in 8 patients (80%) in contrast to only 1 patient (10%) on metoprolol alone and 4 patients (40%) on mexiletine alone. In 5 patients (71%) ventricular tachycardia was abolished. The number of couplets was reduced from 51 +/- 39 to 1.9 +/- 2.4 (p less than 0.01) and total premature ventricular beats from 7790 +/- 9047 to 597 +/- 515 (p = 0.06). Combination therapy was well tolerated without proarrhythmia or precipitation of congestive heart failure. It is concluded that low-dose mexiletine combined with metoprolol is effective in suppressing ventricular arrhythmias in selected patients, and enhances the antiarrhythmic effect of either drug alone without significant side effects.