Heit 2000.

Methods	Study design: Randomised, double‐blind, placebo‐controlled trial Country: US Setting: Multicentre (33 centres); hospital and home; November 1994 to November 1997 Intention‐to‐treat: Yes For the purposes of our analyses we used all participants randomised, as reported by the study authors
Participants	Number randomised: Total n = 1195 (Extended LMWH n = 607; Placebo n = 588) Exclusions post randomisation: Unclear Losses to follow up: Unclear Age mean years (SD): Extended LMWH 65 (11); placebo 66 (11) Sex M/F: Extended LMWH 265/342; placebo 275/313 Inclusion criteria: Aged 18 years or older; received elective primary or revision unilateral total hip replacement, primary unilateral or bilateral total knee replacement Exclusion criteria: 'Pregnant, lactating or women of childbearing age; patients with clinical bleeding disorder; uncontrolled hypertension' severely impaired hepatic or renal function; active alcohol or drug abuse; patients who could not comply with home injections or complete a 10‐week post‐op follow‐up; patients receiving warfarin or thrombolytic therapy; had a major surgery within previous seven days; had major orthopaedic surgery involving lower extremities in previous six weeks; history of substantial internal bleeding, active peptic ulcer, myocardial infarction or stroke; intracranial or intraocular surgery in previous eight weeks; patients planning to undergo staged bilateral total knee replacement with anticipated interval of less than 10 weeks; hypersensitivity to heparin, pork products, metabisulphite, methylparaben or propylparaben; weight great than 120 kg; prolonged activated partial thromboplastin time or prothrombin time at baseline; baseline platelet count less than 100 x 109/L; history of VTE; current use of dextran sulphate, desmopressin acetate, other LMWH, oral anticoagulants, thrombolytic agents or external pneumatic compression
Interventions	Treatment: Ardeparin sodium 100 anti‐Xa IU/kg weight, subcutaneous injections, daily, starting within 24 hours after surgery Control: Four to 10 days ardeparin sodium 100 anti‐Xa IU/kg weight (starting within 24 hours after surgery), daily, subcutaneous injection, followed by placebo injections from time of discharge Duration: Six weeks after surgery
Outcomes	Primary: Incidence of symptomatic, objectively documented DVT or PE or death Secondary: The incidence of major and minor bleeding and thrombocytopenia Bleeding definitions: Major bleeding ‐ overt bleeding associated with haemoglobin decrement of at least 20 g/L or transfusion of at least 2 units of blood products, any intracranial, retroperitoneal, intraocular or mediastinal bleeding that occurred after at least one dose of post‐discharge study drug Minor bleeding ‐ overt bleeding not meeting the criteria for major bleeding
Notes	Funding: Wyeth‐Ayerst Research, Philadelphia, US ‐ performed statistical analysis, data interpretation and manuscript preparation done by writing committee, sponsor did not have prior right of approval for final manuscript publication Method of VTE evaluation/confirmation: Compression duplex ultrasonography or venography, ventilation perfusion lung scanning or pulmonary angiography
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Stratified by clinical centre, type of surgery and history of VTE; block randomisation derived from a randomisation table
Allocation concealment (selection bias)	Low risk	Allocation done in consecutively numbered, sealed envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind phase of study achieved by giving placebo injections in identical Tubex cartridges containing 0.5 mL ardeparin sodium or placebo (sodium chloride solution)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcomes assessed by blinded, central adjudication committee
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for, although > 15% withdrew in both groups
Selective reporting (reporting bias)	Low risk	All outcomes reported on
Other bias	Low risk	No indication of other bias