title: Evaluation of warfarin management with international normalized ratio self-testing and online remote monitoring and management plus low-dose vitamin k with genomic considerations: a pilot study.
abstract: OBJECTIVE
  As better international normalized ratio (INR) control and self-testing reduce events in warfarin-treated patients, and vitamin K supplementation may improve INR control, our primary objective was to evaluate the effect of a system combining frequent INR self-testing with online remote monitoring and management (STORM₂) and low-dose vitamin K supplementation on INR control; our secondary objectives were to assess the impact of STORM₂ on clinician time and to evaluate the influence of pharmacogenomics on INR stability and warfarin dose after vitamin K supplementation.
  
  
  METHODS
  Prospective pre- and postintervention study.
  
  
  METHODS
  Freestanding clinical research center.
  
  
  METHODS
  Fifty-five patients treated with long-term warfarin therapy who were referred from four anticoagulation clinics and seven medical practices.
  
  
  METHODS
  All patients performed weekly INR self-testing and received vitamin K 100 µg/day and online anticoagulation management for 1 year.
  
  
  RESULTS
  INR control and time required for anticoagulation management were assessed, and an analysis of warfarin dosing and INR stability by genetic polymorphism subgroup (vitamin K epoxide reductase complex 1 [VKORC1] and cytochrome P450 2C9 isoenzyme) was performed; vitamin K product content was also analyzed. The percentage of time that the INR is within the time in therapeutic range (TTR) improved from 56% before the intervention to 81% after the intervention (p<0.0001), and time spent at extreme INR values of lower than 1.5 or higher than 5 was reduced from 3.1% to 0.4% (p=0.01). Clinician time was less than 10 minutes per four patient visits per month. Genetic polymorphisms did not correlate with INR stability or the increase in warfarin dose after vitamin K supplementation. The content of the vitamin K product, however, was only 34-76% of the labeled amount. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the genomic-based dosing chart in the warfarin package insert.
  
  
  CONCLUSIONS
  The 25% point improvement in TTR with STORM₂ is a greater improvement than reported previously with other efforts to improve TTR. STORM₂ required a minimum amount of clinician time. Pharmacogenomics were not predictive of improved INR control or the magnitude of the warfarin dose after vitamin K supplementation, although the content of the product was unreliable. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the product information. The potential clinical impact of improved INR control with this method warrants comparisons with conventionally managed warfarin and with the new oral anticoagulants.
authors.affiliation: College of Pharmacy, The University of Texas, Austin, Texas; School of Medicine, The University of Texas Health Science Center, San Antonio, Texas; Genesis Clinical Research, San Antonio, Texas; ClotCare.org, San Antonio, Texas.
authors.forename: Henry I
authors.initials: HI
authors.lastname: Bussey
authors.forename: Marie
authors.initials: M
authors.lastname: Bussey
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Bussey-Smith
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Frei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D019468:Disease Management; D016903:Drug Monitoring / Q000379:methods / Q000592:standards*; D005260:Female; D023281:Genomics / Q000379:methods / Q000592:standards*; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods / Q000592:standards*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D058998:Remote Sensing Technology / Q000379:methods / Q000592:standards; D012648:Self Care / Q000379:methods / Q000592:standards*; D014812:Vitamin K / Q000008:administration & dosage*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin
keywords: anticoagulation; cost; genomics; home INR monitoring; self-testing; vitamin K; warfarin