Combination of procainamide and quinidine for better tolerance and additive effects for ventricular arrhythmias

The efficacy and tolerance of quinidine and procainamide used individually and in combination were studied in 19 patients with frequent ventricular premature complexes (VPCs). During single-drug treatment, the maximum tolerated dose of quinidine without extracardiac dose-related side effects was 1.6 ± 0.21 g/day and that of procainamide was 4.1 ± 1.05 g/day. During combination therapy with smaller doses (p < 0.05) of quinidine (1.16 ± 0.26 g/day) and procainamide (2.80 ± 0.98 g/day), no patient had side effects. Before treatment, all patients had frequent (more than 60 per hour) VPCs and 17 had ventricular tachycardia on Holter monitoring. The frequency of VPCs was reduced to 22 ± 19% with quinidine, 47 ± 40% with procainamide and 9 ± 11% with combination therapy (p < 0.05, combination vs procainamide or quinidine alone). Individually, an effective regimen (more than 83% reduction of VPCs and abolition of ventricular tachycardia) was found in 5 patients (26%) receiving quinidine alone at maximal tolerated dose, in 4 (21%) receiving procainamide alone at maximal tolerated dose, and in 14 (74%) receiving combination therapy (p < 0.01 vs quinidine or procainamide). Thus, the antiarrhythmic effects of quinidine and procainamide are additive. When quinidine or procainamide is ineffective because dose-related extracardiac side effects limit the maximal tolerated dose, combination therapy in smaller and tolerable doses avoids side effects and is more effective than either drug alone at the maximal tolerated dose.