Combination of tocainide and quinidine for better tolerance and additive effects in patients with coronary artery disease

The efficacy and tolerance of tocainide used alone and in combination with quinidine were studied in 20 patients with coronary artery disease and frequent (≥30/h) ventricular premature complexes. Holter electrocardiographic monitoring was performed at baseline and during therapy with tocainide alone, quinidine alone and a combination of tocainide and quinidine. During single drug therapy, the dose of tocainide was 1,680 ± 437 mg/day and that of quinidine was 1,340 ± 235 mg/day. During combination therapy, with smaller doses of tocainide (1,350 ± 394 mg/day) and quinidine (1,060 ± 268 mg/day) in many patients, no patient had side effects. At baseline before therapy, the mean ventricular premature complexes/h were 629 ± 567, couplets/h were 23.9 ± 29.7 and nonsustained ventricular tachycardias/ 24 h were 60.5 ± 152.2. Compared with baseline values (100%), the frequency of ventricular premature complexes was reduced to 33 ± 44% with quinidine, 39 ± 30% with tocainide and 10 ± 16% with combination therapy (p < 0.01 for combination versus quinidine or tocainide alone; p = NS for quinidine versus tocainide). Individually, an effective regimen (>83% reduction of ventricular premature complexes and abolition of non-sustained ventricular tachycardia) was found in 3 (15%) of 20 patients receiving tocainide alone, in 6 (30%) receiving quinidine alone and in 16 (80%) receiving combination therapy (p < 0.01 for tocainide versus combination, quinidine versus combination; p = NS for tocainide versus quinidine).Thus, the antiarrhythmic effects of quinidine and tocainide are additive. A combination of quinidine and tocainide in smaller and well tolerated doses may avoid dose-related side effects and is more effective than either drug used alone at higher doses. Therefore, when quinidine or tocainide is ineffective because dose-related side effects limit the maximal tolerated dose, combination therapy in smaller and tolerable doses may avoid side effects and may be more effective than either drug alone at the maximal tolerated dose

949-101 Circadian Variation of Ventricular Arrhythmias is Abolished by Propranolol

A prospective study investigated whether there is a circadian variation of ventricular arrhythmias in elderly patients (pts) with heart disease before and after propranolol and no antiarrhythmic (AA) drug. Follow-up 24-hour ambulatory electrocardiograms were obtained at a median of 6 months (range 2 to 12) in 221 elderly pts. mean age 81±8 years. with heart disease (64% with prior myocardial infarction and 36% with hypertensive heart disease) and complex ventricular arrhythmias randomized to propranolol 85±28 mg daily (112 pts) or to no AA drug (109 pts). The average number of premature ventricular complexes (PVCs)/hourwas reduced &gt;70% in 80 of 112 pts (71%) treated with propranolol and in 27 of 109 pts (25%) treated with no AA drug (p &lt; 0.001). Double harmonic regression models showed a significant circadian variation of the maximal number of PVCs before no AA drug (p=0.002, R2=57%, adjusted R2=49%). after no AA drug (p &lt; 0.0001. R2=76%. adjusted R2=71%). and before propranolol (p=0.002, R2=57%, adjusted R2=48%). but not after propranolol (p=0.073. R2=35%, adjusted R2=21%). The primary peak incidence of PVCs in pts before and after no AA drug and before propranolol occurred between 7 a.m. and 12 p.m. The secondary peak incidence of PVCs in pts before and after no AA drug occurred between 6 p.m. and 9 p.m. The secondary peak incidence of PVCs in pts before propranolol occurred between 7 p.m. and 8 p.m. These data show that there is a circadian variation of the maximal number of PVCs in elderly pts with heart disease which is abolished by propranolol