title: Prolonged outpatient vitamin K antagonist use and risk of venous thromboembolism in patients undergoing total hip or knee replacement.
abstract: BACKGROUND
  Long-term risk of venous thromboembolism (VTE) following total hip or knee replacement (THR/TKR) compared with controls has not been studied extensively, and the long-term influence of outpatient anticoagulant use on VTE risk remains unknown. The objectives were to evaluate long-term VTE risk following THR/TKR compared with matched controls, and to investigate effect modification by prolonged outpatient vitamin K antagonist use.
  
  
  METHODS
  A Danish retrospective nationwide cohort study was conducted. All patients undergoing primary THR/TKR (n = 95,227) between 1998 and 2007 were selected, each matched by age, sex and region with three controls (no THR/TKR). Patients were stratified by prolonged outpatient vitamin K antagonist use in the previous 3 months (in a time-dependent manner). All subjects were followed for VTE, and Cox models were used to calculate disease and medication history adjusted hazard ratios (HRs).
  
  
  RESULTS
  Within 6 weeks following surgery, a 13-fold increased risk of VTE was found for THR (adj. HR 12.9; 95% CI 11.2-14.7), and a 14-fold elevated risk for TKR (adj. HR 13.6; 95% CI 11.0-16.7), compared with matched controls. The risk remained substantially increased for at least 4 months following THR/TKR. Within this period, prolonged outpatient vitamin K antagonist use reduced the increase in VTE risk by 69% for THR and 54% for TKR.
  
  
  CONCLUSIONS
  The risk of VTE remains substantially elevated for at least 4 months following THR/TKR; this is well beyond the recommended duration of anticoagulant use. The increase in VTE risk is less pronounced in prolonged outpatient vitamin K antagonist users.
authors: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, the Netherlands; Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: A
authors: A
authors: Lalmohamed
authors: P
authors: P
authors: Vestergaard
authors: P A F
authors: PA
authors: Jansen
authors: E L
authors: EL
authors: Grove
authors: A
authors: A
authors: de Boer
authors: H G M
authors: HG
authors: Leufkens
authors: T P
authors: TP
authors: van Staa
authors: F
authors: F
authors: de Vries
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012189:Retrospective Studies; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000209:etiology*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K