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

Abstract

Summary: 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 nonsustnined 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 arrhythniias in 8 patients (80%) in contrast to only 1 patient (10%) on metoprolol alone and 4 patients (40%) on mexiletine alone. In 5 patients (7 1 %) ventricular tachycardia was abolished. The number of couplets was reduced from 51 f 3 9 to 1.9k2.4 (p<O.Ol) and total premature ventricular beats from 7790k9047 to 597k515 (p=O.O6). Combination therapy was well tolerated without proarrhythrnia 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.

Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review

“… 49 , 54 , 57 , 58 , 62 , 65 , 66 , 97 , 125 , 126 , 139 , 155 , 180 , 181 , 189 In all of the studies reporting on left ventricular ejection fraction, 14 (93.3%) of the studies (475 of 476 patients) showed no negative effects of mexiletine on left ventricular ejection fraction. 49 , 54 , 57 , 58 , 62 , 65 , 66 , 97 , 125 , 126 , 155 , 180 , 181 , 189 Three (20%) studies comprising 36 patients reported on right ventricular ejection fraction, and none of these studies demonstrated a decrease in right ventricular ejection fraction. 66 , 125 , 126 …”

“…In 40 (18%) studies, worsening or not worsening of arrhythmias is actively mentioned. 27 , 31 , 34 , 38 , 39 , 41 , 50 , 54 , 55 , 57 , 58 , 60 , 62 , 64 , 68 , 75 , 76 , 85 , 87 , 90 , 106 , 118 , 128 , 129 , 138 , 141 , 151 , 154 , 161 , 164 , 166 , 174 , 175 , 183 , 201 , 207–209 , 213 , 218 In total, in this subset of 40 studies, in 137 of 2173 (6.3%) patients, the arrhythmia worsened after start of mexiletine.…”