title: A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naïve Patients with Non-Valvular Atrial Fibrillation.
abstract: Genotype-guided warfarin dosing have been proposed to improve patient’s management. This study is aimed to determine whether a CYP2C9- VKORC1- CYP4F2-based pharmacogenetic algorithm is superior to a standard, clinically adopted, pharmacodynamic method. Two-hundred naïve patients with non-valvular atrial fibrillation were randomized to trial arms and 180 completed the study. No significant differences were found in the number of out-of-range INRs (INR<2.0 or >3.0) (p = 0.79) and in the mean percentage of time spent in the therapeutic range (TTR) after 19 days in the pharmacogenetic (51.9%) and in the control arm (53.2%, p = 0.71). The percentage of time spent at INR>4.0 was significantly lower in the pharmacogenetic (0.7%) than in the control arm (1.8%) (p = 0.02). Genotype-guided warfarin dosing is not superior in overall anticoagulation control when compared to accurate clinical standard of care.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01178034.
authors.affiliation: Department of Cardiac, Thoracic, and Vascular Sciences University of Padova, Padova, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Pengo
authors.affiliation: Department of Medicine-DIMED, University of Padova, Padova, Italy.|Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Zambon
authors.affiliation: Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fogar
authors.affiliation: Department of Medicine-DIMED, University of Padova, Padova, Italy.|Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Padoan
authors.affiliation: Department of Cardiac, Thoracic, and Vascular Sciences University of Padova, Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nante
authors.affiliation: Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Pelloso
authors.affiliation: Department of Medicine-DIMED, University of Padova, Padova, Italy.|Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Moz
authors.affiliation: Department of Cardiac, Thoracic, and Vascular Sciences University of Padova, Padova, Italy.
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.affiliation: Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Groppa
authors.affiliation: Department of Medicine-DIMED, University of Padova, Padova, Italy.|Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Dania
authors.initials: D
authors.lastname: Bozzato
authors.affiliation: Department of Cardiac, Thoracic, and Vascular Sciences University of Padova, Padova, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Tiso
authors.affiliation: Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gnatta
authors.affiliation: Department of Cardiac, Thoracic, and Vascular Sciences University of Padova, Padova, Italy.
authors.forename: Gentian
authors.initials: G
authors.lastname: Denas
authors.affiliation: Department of Cardiac, Thoracic, and Vascular Sciences University of Padova, Padova, Italy.
authors.forename: Seena
authors.initials: S
authors.lastname: Padayattil Jose
authors.affiliation: Department of Medicine-DIMED, University of Padova, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Padrini
authors.affiliation: Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Basso
authors.affiliation: Department of Medicine-DIMED, University of Padova, Padova, Italy.|Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000072470:Cytochrome P450 Family 4; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases / Q000378:metabolism; D014859:Warfarin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases