Initial and long-term outpatient experience with pirmenol for control of ventricular arrhythmias

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Abstract
Pirmenol, a new class IA antiarrhythmic agent, has shown promise in short-term trials, but long-term efficacy has not been documented. We thus evaluated 11 patients with frequent (≥60/h) premature ventricular complexes (PVC) given oral pirmenol for 25–727 days. Ten of 11 patients entering the long-term open trial had shown ≥70% (mean 83%) PVC suppression during in-hospital pirmenol dose ranging. Long-term pirmenol was given in divided doses of 100–600 mg/day. Mean PVC frequency during baseline was 13,078/24h (range, 3,218–32,718); couplets averaged 481/24h (1–2,829) and runs 45/24h (0–334). Ambulatory monitoring was performed at 1, 3, 6, and 12 months, then semiannually. Mean absolute PVC suppression at 1 month averaged 75% (p≤0.02). Median individual percentage PVC suppression was 94%. During the first 3 months, 8 patients (73%) continued to show a favorable response (≥70% suppression), and 3 had arrhythmia recurrence and were dropped. One responder was withdrawn after the onset of paroxysmal atrial fibrillation, and another early responder was withdrawn after 3 months because of arrhythmia relapse. Six patients have been treated for over 1 year, with 99% mean PVC suppression. Mean couplet and run frequencies at 1 month decreased by means of 76% (p≤0.05) and 92% (p=0.001) respectively. At 1 year, couplets were suppressed 99.8% and runs by 99.7% in the 6 patients remaining on pirmenol. Mean QT interval increased slightly (7.1%,p<0.05); mean PR and QRS intervals were unchanged. Plasma pirmenol concentrations averaged 1.49 µg/ml at clinic evaluations, 1.72 µg/ml in responders vs 1.08 µg/ml in nonresponders. Inade-quate plasma drug concentrations may be one cause for arrhythmia recurrence. Adverse effects were minimal. Thus, oral pirmenol is a safe and effective agent for long-term outpatient management of complex ventricular arrhythmias in selected patients.