bioRxivPharmacology & Toxicology
Multicenter Analysis of Dosing Protocols for Sotalol Initiation
M. Biswas, A. E. Levy, R. Weber, K. Tarakji, M. Chung, P. A. Noseworthy, C. Newton-Cheh, M. A. Rosenberg
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.
- organism: human
- assay: clinical cohort / trial
- research focus: drug response / drug discovery
- approach: statistical model
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