Beta blockers in combination with class I antiarrhythmic agents

Abstract

The hemodynamic and antiarrhythmic interactions between nadolol and a commonly used class I antiarrhythmic agent, quinidine or procainamide, were evaluated in 18 patients with ventricular arrhythmias in a double-blind, parallel study. Patients qualified for entry into the study if their ventricular arrhythmias remained poorly controlled (≥10 ventricular premature complexes/hr) with the class I agent alone and they had a left ventricular ejection fraction > 30%. Patients received their usual therapeutic doses of quinidine or procainamide throughout the study, which consisted of 3 treatment periods; a 2-week placebo treatment period, a 2-week open-label oral nadolol dose titration period, during which the dosages of nadolol were gradually increased from 40 mg daily to a maximum tolerated dose up to 120 mg daily, and a 4-week randomized, parallel comparison period during which patients were treated with either a class I agent alone or a combination of a class I agent and nadolol. Left ventricular ejection fractions by radionuclide ventriculography and 24-hour ambulatory electrocardiographic (Holter) recordings were obtained at the end of each treatment period. A positive treatment response was defined as ≥ 75% reduction in ventricular premature complex frequency. During the dose titration phase, combination therapy with nadolol (mean dose 94 mg daily) and class I agents produced a mean decrease in ventricular premature complexes of 79% (p < 0.01), and a mean decrease in ventricular couplets of 95% (p < 0.01). A positive response was observed in 57% of patients treated with nadolol plus a class I agent. After 4 weeks of double-blind therapy, 63% of patients receiving combination therapy were treated successfully compared with 29% of patients receiving class I agents alone. The frequency of ventricular premature complexes was decreased by 92% in patients receiving combination therapy, while ventricular premature complex reduction was only 19% in patients receiving class I agents alone. Similarly, combination therapy decreased ventricular couplets by 91%, while patients treated with class I agents alone showed a mean increase of 156% in ventricular couplets. No patient developed any evidence of left ventricular dysfunction, the left ventricular ejection fraction remained unchanged throughout the study and none of the patients were discontinued from the study because of serious side effects. Combination therapy with nadolol and class I antiarrhythmic agents is safe and effective in the management of patients whose ventricular arrhythmias are refractory to therapeutic doses of class I agents alone.