Use of a Simplified Nomogram to Individualize Digoxin Dosing versus Standard Dosing Practices in Patients with Heart Failure

• Published in: Pharmacotherapy 2014-11, Vol.34 (11), p.1121-1131
• Main Authors: DiDomenico, Robert J., Bress, Adam P., Na-Thalang, Kwanta, Tsao, Yvonne Y., Groo, Vicki L., Deyo, Kelly L., Patel, Shitalben R., Bishop, Jeffrey R., Bauman, Jerry L.
• Format: Article
• Language: English
• Subjects: Academic Medical Centers; Aged; Amino Acid Substitution; ATP Binding Cassette Transporter, Sub-Family B - genetics; Biological and medical sciences; Cardiology. Vascular system; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - blood; Cardiotonic Agents - pharmacokinetics; Cardiotonic Agents - therapeutic use; Chicago; digoxin; Digoxin - administration & dosage; Digoxin - blood; Digoxin - pharmacokinetics; Digoxin - therapeutic use; Dose-Response Relationship, Drug; dosing nomogram; Drug Monitoring; Female; Gene Frequency; Genetic Association Studies; Heart; heart failure; Heart Failure - etiology; Heart Failure - prevention & control; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Historically Controlled Study; Humans; Male; Medical sciences; Middle Aged; Nomograms; Outpatient Clinics, Hospital; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; Precision Medicine; Ventricular Dysfunction, Left - blood; Ventricular Dysfunction, Left - drug therapy; Ventricular Dysfunction, Left - genetics; Ventricular Dysfunction, Left - physiopathology
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1002/phar.1480

Study Objectives To compare the frequency of achieving a therapeutic serum digoxin concentration (SDC), defined as 0.5–0.9 ng/ml, by using a simplified nomogram to individualize digoxin dosing with standard dosing practices in patients with heart failure, and to characterize the relationship between genetic polymorphisms of the ABCB1 gene and SDC. Design Prospective study with a historical control group. Setting Outpatient care center of an urban academic medical center. Patients A total of 131 adults with heart failure due to left ventricular dysfunction who were treated with digoxin. Intervention Digoxin doses were determined either by the dosing nomogram (65 patients) or standard care (SC; 66 patients) by using historical controls who were randomly selected from a list of SDCs obtained from laboratory records and who had their digoxin doses determined by standard dosing practices. Measurements and Main Results The primary end point was the proportion of patients achieving a steady‐state SDC of 0.5–0.9 ng/ml; secondary end points were mean SDC and proportion of patients achieving a steady‐state SDC lower than 1.0 ng/ml. Postdistributive steady‐state SDCs were measured 2–4 weeks after digoxin dosage adjustment or initiation. Therapeutic SDCs were achieved with similar frequency in both groups (38.7% in the nomogram group vs 34.5% in the SC group, p=0.65); however, more patients in the nomogram group had SDCs lower than 1.0 ng/ml than in the SC group (85.0% vs 44.9%, p