Comparison of individual and combined effects of procainamide and amiodarone in patients with sustained ventricular tachyarrhythmias

Abstract

To compare the individual and combined electrophysiological effects of amiodarone and procainamide, 35 patients with sustained ventricular arrhythmias underwent programmed stimulation in the control state, after procainamide (mean concentration, 8.7 ± 2.8 μg/ml), after 13 ± 2 days of amiodarone (1,400 mg/day x 7 days, then 400 mg/day), and after amiodarone with procainamide (mean procainamide concentration, 7.8 ± 2.2 μg/ml). Sustained ventricular tachycardia (VT) was inducible in all 35 patients during treatment with procainamide alone and with amiodarone alone. Procainamide and amiodarone similarly increased the VT cycle length (+68 vs. +61 msec), the corrected QT interval (+63 vs. +49 msec), and the ventricular effective refractory period measured at paced cycle lengths of 600-550 msec (+23 vs. +21 msec) and 400 msec (+25 vs. +23 msec). Procainamide had a more pronounced effect on QRS duration than amiodarone during sinus rhythm (+18 vs. +8 msec, p < 0.01) and during paced cycle lengths of 600-550 msec (+32 vs. +23 msec, p < 0.01) and 400 msec (+37 vs. +28 msec, p < 0.1) but a similar effect on the QRS duration during VT (+32 vs. +29 msec). During combination therapy, VT initiation was prevented in only two (6%) patients. The combination therapy produced a greater increase (p < 0.001) than individual therapy in all the electrophysiological invervals assessed, with the exception of the sinus cycle length. On each drug regimen, a cycle length-dependent increase (p < 0.05) in paced QRS duration was noted (400 more than 600-550 msec). The sum of the electrophysiological changes in conduction and refractoriness of the individual agents correlated with the change attributable to combination drug therapy (r = 0.58-0.81, p < 0.01). The relation of the sum of the change in the cycle length of morphologically similar VT after each agent alone to the change with the combination therapy could be expressed by the regression equation of combined effect = 0.67 x sum of the individual effects + 40 msec, with r = 0.85, p < 0.001. In summary, with the dosing regimen described, 1) procainamide and amiodarone have similar effects on the cycle length of morphologically similar VT and on indexes of refractoriness, but procainamide has a greater effect on paced QRS duration; 2) amiodarone with procainamide does not affect the ability to initiate VT; and 3) knowledge of the change in cycle length of VT after treatment with the individual agents alone permits estimation of the cycle length of morphologically similar VT on the combination therapy.