Evaluation of disopyramide and mexiletine used alone and in combination for ventricular arrhythmias in patients with and without overt heart disease.
The efficacies and side effects of disopyramide and mexiletine used alone and in combination were assessed in 29 patients with chronic ventricular arrhythmias. In combination therapy, one half or two thirds of the conventional doses of each drug were administered. Each patient underwent Holter electrocardiographic monitoring during 4 different periods: baseline, disopyramide alone, mexiletine alone and combination of the two drugs. The mean baseline number of ventricular premature complex per hour was 783 +/- 521 (mean +/- SD), which was significantly reduced with all three therapies. Disopyramide alone significantly reduced the ventricular premature complex frequency in patients with organic heart disease (P less than 0.05), but did not significantly reduce the ventricular premature complex frequency in patients with no apparent heart disease. In contrast, mexiletine alone significantly decreased the ventricular premature complex frequency in no apparent heart disease patients (P less than 0.05), but did not significantly reduce the ventricular premature complex frequency in organic heart disease patients. With disopyramide alone, patients having a significant reduction in ventricular premature complexes (greater than or equal to 83% reduction in ventricular premature complexes) or elimination of ventricular tachycardias tended to be more frequently found in organic heart disease than in no apparent heart disease. The opposite was observed with mexiletine alone. QTc interval with disopyramide alone was significantly prolonged, and the prematurity index of ventricular premature complexes was significantly lowered as compared to mexiletine alone or combination therapy (P less than 0.01 for disopyramide versus mexiletine; P less than 0.05 for disopyramide versus combination therapy). During combination therapy, no patients withdrew from the study due to side effects. However, 3 patients receiving single drug therapy withdrew from the study due to severe side effects. Consequently, disopyramide is suggested to be more effective on ventricular premature complexes in organic heart disease than in no apparent heart disease patients, whereas the opposite was true for mexiletine. A combination of disopyramide and mexiletine in smaller doses may provide almost the same or enhanced antiarrhythmic effects, no aggravation of electrocardiographical parameters and less incidence of side effects when compared to the conventional dose of each drug alone.
Tanabe
T
T
Department of Cardiology, Tokai University School of Medicine, Isehara, Japan.
Takahashi
K
K
Yoshioka
K
K
Goto
Y
Y
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D005117:Cardiac Complexes, Premature / Q000150:complications / Q000188:drug therapy*; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology; D002312:Cardiomyopathy, Hypertrophic / Q000503:physiopathology; D004206:Disopyramide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004338:Drug Combinations; D004341:Drug Evaluation; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology; D011660:Pulmonary Heart Disease / Q000503:physiopathology
D004338:Drug Combinations; D008801:Mexiletine; D004206:Disopyramide