title: Randomised trial of a clinical dosing algorithm to start anticoagulation with phenprocoumon.
abstract: OBJECTIVE
  Prospective validation of two algorithms for the initiation of phenprocoumon treatment.
  
  
  METHODS
  Inpatients with new-onset anticoagulation were randomised to one of two computer assisted dosing algorithms, or to a control arm. The primary outcome measure was the time to achieve therapeutic anticoagulation without overshooting (INR >4.0 within 10 days). Secondary outcomes included overshooting INR values, death, or bleeding within 30 days. In addition, predictors of the dosing algorithms for the loading dose and the maintenance dose including genetic parameters were reassessed.
  
  
  RESULTS
  105 patients were randomised to arm A, 103 to arm B and 93 to the control arm. Arms A and B needed a median of 7 days to reach a therapeutic INR, arm C 6 days (p = 0.5). Overshooting INR was observed in 3.8%, 1.9% and 4.3% respectively (p = 0.6). Bleeding was found in 0%, 1.9%, and 5.4% (p = 0.06) and 30-day mortality was 0%, 1%, and 2.2% respectively (p = 0.2). VKORC1:c.-1639 G>A was associated with lower loading doses whereas VKORC1:c.-1453 G>A needed higher doses. VKORC1:c.-1639 G>A was also associated with lower maintenance doses.
  
  
  CONCLUSIONS
  Both algorithms allow safe initial dosing of phenprocoumon but they are not superior to anticoagulation by trained physicians. Dosing aids for coumarins with readily available clinical parameters may nevertheless be helpful for use in polymorbid hospitalised patients. Clinical data and the INR-response to treatment provides powerful information and delaying initiation of anticoagulation while awaiting genetic tests is not expected to increase drug safety.
authors.affiliation: Hospital Pharmacy, University Children's Hospital, Zurich, Switzerland. Angela.Caduff@kispi.uzh.ch
authors.forename: Angela
authors.initials: A
authors.lastname: Caduff Good
authors.forename: Daniel
authors.initials: D
authors.lastname: Nobel
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
authors.forename: Christof
authors.initials: C
authors.lastname: Geisen
authors.forename: Samuel
authors.initials: S
authors.lastname: Henz
mesh_terms: D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage*; D016001:Confidence Intervals; D003374:Coumarins / Q000008:administration & dosage; D054796:Drug Dosage Calculations; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000008:administration & dosage*; D019338:Polypharmacy
chemical_list: D000925:Anticoagulants; D003374:Coumarins; C030123:coumarin; D010644:Phenprocoumon