Dr. DiDomenico, Pharm.D., BCPS-AQ Cardiology, FCCP, HFSA, FACC is an Associate Professor in the Department of Pharmacy Practice at the University of Illinois at Chicago (UIC), a member of the Center for Pharmacoepidemiology and Pharmacoeconomic Research, and a Cardiovascular Clinical Pharmacist at the University of Illinois Hospital & Health Sciences System with an inpatient cardiology practice site. In this video Dr. Dimonenico talks about Digoxin Dosing in Heart Failure: A Simplified Nomogram Versus Standard Care.
Link to Study-
Digoxin, a medicine used to treat heart failure, hasn't had its dose procedures updated in decades, despite recent evidence suggesting that blood levels of digoxin attained using standard dosing practices may raise the risk of adverse outcomes. We created a simple dosage method that targets lower digoxin blood levels, which have been linked to better results when compared to higher blood levels. The goal of this study is to see if this simplified dosing method is more effective in lowering blood levels than normal digoxin dosing practices, and if digoxin dosing can be further enhanced by incorporating patients' genetic information, which is thought to alter the drug's characteristics.
Digoxin is used as an additional medication in patients who have left ventricular dysfunction and symptoms of heart failure despite receiving normal treatment. Because lower serum levels in this range have been associated with improved survival whereas higher serum levels have been associated with increased mortality, the therapeutic range for digoxin in patients with heart failure has recently been redefined to a narrower therapeutic window (0.5 - 0.9 ng/ml). Dosing procedures, on the other hand, have not been modified to match the expanded digoxin therapeutic range. Using historical data, we devised a simpler digoxin dose nomogram for patients with heart failure in order to reach serum digoxin concentrations (SDC) within the revised therapeutic range. The long-term goal of this research is to prospectively confirm our digoxin dose nomogram's capacity to achieve desired SDC and give doctors with a simple tool to optimize digoxin dosing in heart failure patients. Because digoxin is a substrate of the efflux pump p-glycoprotein (pGP), and genetic polymorphisms in the MDR1 gene (which regulates pGP expression) have shown conflicting results in terms of digoxin pharmacokinetics, we'll look into the impact MDR1 functional gene variants may have on digoxin dosing. A total of 170 patients with symptomatic heart failure treated with digoxin will be included in this study, which will compare steady-state SDC in a prospective group of patients dosed according to our nomogram to a historical control group whose digoxin dose was derived from standard dosing practices. We'll also look into genetic variants in the MDR1 gene that have been linked to digoxin pharmacokinetics. The study's main goals are to compare the percentage of patients in each group who achieve steady-state SDC in the desired range of 0.5-0.9 ng/ml, characterize the relationship between genetic variability in the MDR1 gene and digoxin dosing, and update our digoxin dosing nomogram to account for the clinical and genetic variability that has been shown to have the most impact on digoxin dosing. The study's rationale is that lower digoxin doses are recommended because lower SDC is linked to better survival. In order to improve clinical outcomes and reduce the risk of adverse events, digoxin dosing regimens must be revised to reflect these recommendations and account for genetic heterogeneity of the MDR1 gene. The precise goals of this research are to address these issues:
Aim 1: Compare steady-state SDC produced with our dosing nomogram to those acquired with current dosing techniques.
Aim 2: Using our digoxin dose nomogram, characterize the link between MDR1 gene genetic diversity and SDC.