title: Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke.
abstract: BACKGROUND
  Patients with certain types of stroke need urgent anticoagulation and it is extremely important for them to achieve fast and stable anticoagulant effect and receive individualized treatment during the initiation of warfarin therapy.
  
  
  METHODS
  We conducted a prospective study among 210 acute stroke patients who had an indication for anticoagulation and compared the impact of CYP2C9 and VKORC1 genotype-guided warfarin dosing (PhG) with fixed dosing (NPhG) on anticoagulation control and clinical outcome between groups.
  
  
  RESULTS
  PhG achieved target INR values earlier, i.e., on average in 4.2 (4.1-4.7, 95% CI) days compared to NPhG (5.2 days [4.7-6.4, 95% CI]) (p = 0.0009), spent a higher percentage of time in the therapeutic INR range (76.3% [74.7-78.5, 95% CI] vs. 67.1% [64.5-69.6, 95% CI] in NPhG), and spent less time overdosed (INR > 3.1) (PhG 0.4 [0.1-0.7, 95% CI], NPhG 1.7 [1.1-2.3, 95% CI] days; p >0.000). PhG reached stable maintenance dose faster (10 [9.9-10.7, 95% CI] vs. 13.9 [13.3-14.7, 95% CI] days in controls; p = 0.0049) and had a better clinical outcome in relation to neurological deficit on admission as compared to NPhG.
  
  
  CONCLUSIONS
  We confirmed that warfarin therapy with genotype-guided dosing instead of fixed dosing reduces the time required for stabilization and improves anticoagulant control with better clinical outcome in early stages of warfarin therapy introduction among acute stroke patients, which is essential for clinical practice.
authors.affiliation: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Šupe
authors.affiliation: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Zdravka
authors.initials: Z
authors.lastname: Poljaković
authors.affiliation: Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Božina
authors.affiliation: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Josip
authors.initials: J
authors.lastname: Ljevak
authors.affiliation: Agency for Medicinal Products and Medical Devices, Zagreb, Croatia.
authors.forename: Viola
authors.initials: V
authors.lastname: Macolić Šarinić
authors.affiliation: Department of Laboratory Diagnostics, Zagreb University Hospital Center, Zagreb, Croatia; Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia. Electronic address: nbozina@kbc-zagreb.hr.
authors.forename: Nada
authors.initials: N
authors.lastname: Božina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; Polymorphisms; Stroke; VKORC1; Warfarin