title: Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective study with a historical control group.
  
  
  METHODS
  Outpatient care center of an urban academic medical center.
  
  
  METHODS
  A total of 131 adults with heart failure due to left ventricular dysfunction who were treated with digoxin.
  
  
  METHODS
  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.
  
  
  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<0.001). Mean daily digoxin doses were lower in the nomogram group (149 ± 67 μg vs 177 ± 74 μg, p=0.02), resulting in lower mean SDCs compared with those in the SC group (0.52 ± 0.30 ng/ml vs 1.12 ± 0.58 ng/ml, p<0.001). Patients in the pharmacogenetic substudy provided blood samples for genotyping of three common ABCB1 single nucleotide polymorphisms: C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642). SDCs were not significantly associated with ABCB1 genotypes.
  
  
  CONCLUSIONS
  Our simplified digoxin dosing nomogram resulted in lower SDCs compared with standard dosing practices but achieved therapeutic SDCs with similar frequency. A greater proportion of patients dosed according to our nomogram had SDCs lower than 1.0 ng/ml, consistent with consensus guidelines. Genetic polymorphisms of the ABCB1 gene were not associated with SDC.
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DiDomenico
authors.forename: Adam P
authors.initials: AP
authors.lastname: Bress
authors.forename: Kwanta
authors.initials: K
authors.lastname: Na-Thalang
authors.forename: Yvonne Y
authors.initials: YY
authors.lastname: Tsao
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Groo
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Deyo
authors.forename: Shitalben R
authors.initials: SR
authors.lastname: Patel
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bishop
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Bauman
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000046:Academic Medical Centers; D000368:Aged; D019943:Amino Acid Substitution; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D002641:Chicago; D004077:Digoxin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D065386:Historically Controlled Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D010044:Outpatient Clinics, Hospital; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D002316:Cardiotonic Agents; D004077:Digoxin
keywords: digoxin; dosing nomogram; heart failure