Bern 2015.

Methods	Prospective, randomised, 3‐arm study
Participants	Total number of participants: 355 Number of participants allocated to each group: variable‐dose warfarin group: 118, fondaparinux group: 118, 1 mg daily warfarin group: 119 Number of participants excluded and/or lost to follow‐up: 2 in variable‐dose warfarin group did not receive allocated intervention, 1 was not analysed; 10 in fondaparinux group did not receive allocated intervention, 6 were not analysed; 7 in 1 mg daily warfarin group did not receive allocated intervention, 6 were not analysed Inclusion criteria: Participants were recruited from among patients over 20 years of age planning elective primary unilateral total hip or knee replacement surgery at an orthopaedic specialty hospital. Exclusion criteria Abnormal platelet count, prothrombin time (PT) or partial thromboplastin time (PTT) Surgery for acute fracture (< 4 weeks), septic joint or extraction arthroplasty History of VTE or documented hypercoagulation syndrome Increased risk of haemorrhage, as from active gastric ulcer or urinary tract bleed within the past year Haemorrhagic stroke; brain, spinal or ophthalmologic surgery in previous 6 months Liver enzymes or bilirubin greater than 2 x normal Decreased renal function with GFR < 30 mL/min Cancer in past year, other than localised cancers of the skin Need for chronic anticoagulation Need for long‐term platelet function suppressive therapy Prior adverse reaction to any of the study drugs Uncontrolled hypertension BMI > 42 Pregnancy
Interventions	ARM A Variable‐dose warfarin: 5.0 mg beginning the night before surgery, followed by 5.0 mg the night of surgery, then variable daily dose (target INR 2.0 to 2.5) until day 28 ± 2 of follow‐up ARM B Fondaparinux: 2.5 mg daily starting 6 or more hours after surgery, but no later than 6 AM the next day, or 6 to 8 hours after epidural catheter removal; continued until day 28 ± 2 of follow‐up ARM C Fixed low‐dose warfarin 1.0 mg daily, beginning 7 days preoperatively, and continued at 1.0 mg daily until day 28 ± 2 of follow‐up
Outcomes	Primary endpoint was composite DVT, PE or death due to VTE. Secondary endpoints included frequency of proximal vs distal DVT, estimated blood loss (EBL) at surgery and haemorrhagic complications.
Notes	Use of adjunctive anticoagulative methods: Patients had early postoperative ambulation. All patients wore pneumatic compression stockings while in‐patients. Elastic compression stockings were prescribed to be used after discharge until follow‐up ultrasonography. Hydroxyethyl starch (HES) 6% was allowed intraoperatively for case‐specific reasons. Use of platelet function suppressive drugs, such as non‐steroidal anti‐inflammatory drugs (NSAIDs), was discouraged but was not prohibited by the protocol.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A member of the pharmacy department pulled randomized cards as prepared by the statisticians" Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote: "A member of the pharmacy department pulled randomized cards as prepared by the statisticians" Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not mentioned Comment: probably not done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Radiology technicians and the radiologists were blinded to patient randomization" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	99.1%, 94.9% and 94.9% of participants in 3 groups completed the study. Comment: probably done
Selective reporting (reporting bias)	Low risk	All endpoints listed in the Methods section were reported. Comment: low risk of bias
Other bias	Low risk	No risk of other bias identified