title: Initiation of rivaroxaban following low molecular weight heparin for thromboprophylaxis after total joint replacement: the Safe, Simple Transitions (SST) study.
abstract: BACKGROUND
  No data are available regarding appropriate strategies for the transition of patients undergoing total hip or knee replacement (THR/TKR) surgery from subcutaneous low molecular weight heparin (LMWH) to rivaroxaban. This study determined the pharmacodynamic effects of rivaroxaban on the first day of administration compared with serial administration in patients who had transitioned to rivaroxaban 22-28 hours after the last once-daily LMWH dose (or 12-18 hours after the last twice-daily LMWH dose).
  
  
  METHODS
  Patients undergoing THR or TKR surgery who had received at least one post-operative LMWH dose were included in this open-label, single-arm, multicentre study. Measurements of anti-Factor Xa activity and prothrombin time were made on the first and third days of daily rivaroxaban administration. The effects of age and renal function on these parameters, and safety and tolerability, were assessed.
  
  
  RESULTS
  Fifty-six patients were enrolled in the Safe, Simple Transitions (SST) study; 52 patients comprised the intention-to-treat population. Mean anti-Factor Xa activity increased slightly but significantly from day 1 to day 3, whereas the area under the concentration-time curve (AUC) was similar on days 1 and 3. Mean prothrombin time was slightly prolonged on day 1 compared with day 3; the AUC was significantly increased (p<0.0001). The pharmacodynamic effects of rivaroxaban were slightly increased in older patients and those with reduced renal function. There were no cases of venous thromboembolism or bleeding and no unexpected adverse events.
  
  
  CONCLUSIONS
  Initiating rivaroxaban approximately 12 or 24 hours after the last LMWH dose (as appropriate) provides a simple, well-tolerated transition strategy for thromboprophylaxis in patients undergoing THR/TKR surgery.
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ 08869-1420, USA. rmills@its.jnj.com
authors.forename: Roger M
authors.initials: RM
authors.lastname: Mills
authors.forename: Richard D
authors.initials: RD
authors.lastname: Berkowitz
authors.forename: C V
authors.initials: CV
authors.lastname: Damaraju
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Jennings
authors.forename: Peter
authors.initials: P
authors.lastname: Wildgoose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban