Multicenter Analysis of Dosing Protocols for Sotalol Initiation

Abstract

Sotalol is a Vaughan-Williams Class III antiarrhythmic medication that is commonly used in the management of both atrial and ventricular arrhythmias. Like others in this class, sotalol carries a risk of the potentially lethal arrhythmia torsade de pointes due to its effect of prolonging the QT interval on ECG. For this reason, many centers admit patients for telemetry monitoring during the initial 2-3 days of dosing. However, despite its widespread use, little information is available about the dosing protocols used during this initiation process. In this multicenter investigation, we examine the characteristics of various dose protocols in 213 patients who initiated sotalol over a 4-year period. Of these patients, over 90% were able to successfully complete the dosing regimen (i.e., were discharged on the medication). Significant bradycardia, excessive QT prolongation, and ineffectiveness were the main reasons for failed completion.We found that any dose adjustment was one of the strongest univariate predictors of successful initiation (OR 6.6, 95%CI 1.3 -32.7, p = 0.021), while initial dose, indication, and resting heart rate or QT interval on baseline ECG did not predict successful initiation. Several predictors of any dose adjustment were identified, and included diabetes, hypertension, presence of pacemaker, heart failure diagnosis, and depressed LV ejection fraction. Using marginal structural models (i.e., inverse probability weighting based on probability of a dose adjustment), we verified that these factors also predicted successful initiation via preventing any dose adjustment, and suggests that consideration of these factors may result in higher likelihood of successful initiation in future investigations. In conclusion, we found that the majority of patients admitted for sotalol initiation are successfully discharged on the medication, often without a single adjustment in the dose. Our findings suggest that several factors predicting lack of dose adjustment could be used clinically to identify patients who could potentially undergo outpatient initiation, although prospective studies are needed to verify this approach. BackgroundSotalol is a Vaughan-Williams (VW) Class III antiarrhythmic agent that is used in the treatment of atrial 1-3 and ventricular arrhythmias 4-8 . Composed of a racemic mix of two isomers, the d and l isomers of sotalol work together to prolong repolarization (d-and l-isomer) along with nonselective beta-blocking properties (l-isomer). This property is significant as use of isolated d-Sotalol was found to be associated with increased mortality in patients with heart failure in the SWORD study 9 , while use of the racemic mixture is generally considered to be safer in this population. Like other VW Class III agents, sotalol displays reverse use dependence properties, in which heart rate and the QT interval are inversely related such that at lower heart rates, the QT interval prolongs 10 . At doses between 160 and 640 mg/day, sotalol increases QT interval by 40 to 100 ms 11 . In a co...