Effectiveness of low-dose nadolol for ventricular arrhythmias

To determine the minimal effective dose of nadolol to suppress frequent ventricular premature complexes (VPCs), 23 patients with at least 30 VPCs/hour on 2 baseline 24-hour Holter recordings were studied. The initial dose of nadolol was 10 mg/day orally, and this dose was doubled at weekly intervals until arrhythmia suppression was achieved, adverse effects appeared, or a maximal dose of 160 mg/day was reached. After each dose level a 24-hour ambulatory Holter monitor was recorded. A pharmacokinetic trial was conducted in patients who responded to nadolol treatment. Frequent VPCs were suppressed at least 75% by nadolol in 11 of 23 patients (48%) and the minimal effective dose was 10 mg/day in 3 patients, 20 mg/day in 4, 40 mg/day in 3 and 80 mg/day in 1 patient. At these doses, minimal steady-state levels of nadolol in serum (Cmin) ranged from 3.9 to 47.0 ng/ml, and these serum concentrations were proportional to the oral dose of nadolol (r = 0.753, p less than 0.001). No relation, however, was observed between Cmin levels and percent reduction of VPCs. Cmin and heart rate changes were comparable between responders and nonresponders, suggesting that the degree of beta blockade was similar between these 2 groups. Adverse reactions were noted in 6 patients, and 2 had an asymptomatic increase in the frequency of VPCs and 1 patient an increase in beats of ventricular tachycardia. This study details the importance of selecting an individualized dose for nadolol for control of ventricular arrhythmias; in more than half of the patients doses of 20 mg/day or less were effective.