Efficacy of combination therapy with mexiletine and a type IA agent for inducible ventricular tachyarrhythmias secondary to coronary artery disease.

The efficacy of combination therapy using a type IA agent (quinidine or procainamide) and a type IB agent (mexiletine) in suppressing inducible sustained ventricular tachyarrhythmias was studied in 23 patients undergoing serial drug testing with programmed stimulation. All patients had coronary artery disease (CAD) with previous myocardial infarction and abnormal left ventricular function (mean ejection fraction 35%). Fifty-five percent of the patients presented with syncope or cardiac arrest. In 19 patients therapy had failed during empiric trials of 1 to 3 antiarrhythmic agents. All 23 patients had inducible sustained ventricular tachyarrhythmias (18 had uniform morphology sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation [VF]) during control electrophysiologic study, and therapy had failed with a type IA agent and mexiletine alone. The combination therapy of mexiletine and the type IA agent prevented induction of any ventricular tachyarrhythmias in 8 of 23 patients. In 15 patients, the combination significantly prolonged the tachycardia cycle length and reduced the symptoms associated with the induced arrhythmia. Patients more likely to respond to the combination had shorter cycle lengths and polymorphic configuration of the control-induced arrhythmia. The increased efficacy of the combination therapy could not be attributed to higher plasma drug levels for the combination, as there was no significant difference in plasma levels for each drug when given alone or in combination. Thus, the increased efficacy most likely reflects a synergistic electropharmacologic effect of the 2 agents.(ABSTRACT TRUNCATED AT 250 WORDS)