Efficacy of intravenous pirmenol hydrochloride for treatment of ventricular arrhythmias: a controlled comparison with lidocaine.

Abstract

Twelve patients with chronic ventricular arrhythmias (PVCs) of frequency greater than 60/h received intravenous pirmenol (150 mg/30 min) according to a single-blind, placebo-controlled protocol. Participating patients had previously been inadequately treated with an average of 3.0 (range, 2–6) antiarrhythmics. Eight of these 12 patients (67%) responded to pirmenol at a level of over 95% PVC suppression (mean suppression in responders, 99.7%). In eight consecutive patients, response to pirmenol was compared with that to lidocaine (250 mg/30 min) in a single-blind random-sequence fashion. Only two of eight patients responded to lidocaine. Mean PVC frequency decreased by 40.4% after lidocaine (p = NS). Five patients (63%) had adverse neurologic reactions, which required early discontinuation of lidocaine in two (25%). In contrast, seven of these eight patients (88%) responded to pirmenol (p < 0.02 versus lidocaine). PVC frequency for this subgroup decreased by 79.8% after pirmenol (p < 0.05). A minor adverse reaction occurred in only one patient (12.5%) (p < 0.05, lidocaine versus pirmenol). Pirmenol was well tolerated hemodynamically, with small increases in diastolic blood pressure and heart rate which remained within the normal range. Electrocardiographic intervals (PR, QRS, QT) were modestly increased at the end of infusion. Mean echocardiographic ejection fractions were unchanged after placebo, pirmenol, and lidocaine infusions. Lidocaine plasma concentrations after infusion averaged 4.4 μg/ml (range, 2.6–7.7). Average pirmenol concentrations of 3.1 μg/ml (range, 2.2–8.2) were achieved: geometric mean elimination half-life was 7.6 h (range, 4.2–16.9). Recurrence of PVCs to 10% of control frequency correlated with a fall in pirmenol concentrations to a mean of 1.3 μg/ml in responders. Pirmenol appears to be a safe and effective antiarrhythmic when administered intravenously. Pirmenol appeared superior to lidocaine in our small group of patients with chronic stable ventricular arrhythmias.