title: Preoperative enoxaparin versus postoperative semuloparin thromboprophylaxis in major abdominal surgery: a randomized controlled trial.
abstract: OBJECTIVE
  To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery.
  
  
  BACKGROUND
  Venous thromboembolism is an important complication following major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity.
  
  
  METHODS
  In this double-blind noninferiority trial, adult patients undergoing major abdominal or pelvic operation under general anesthesia lasting more than 45 minutes were assigned to either daily enoxaparin 40 mg commenced preoperatively or daily semuloparin 20 mg commenced postoperatively, for 7 to 10 days. Patients underwent bilateral leg venography between 7 and 11 days postsurgery. The primary efficacy end point was the composite of any deep vein thrombosis, nonfatal pulmonary embolism, or all-cause death. The primary safety outcome was bleeding. Both were independently adjudicated.
  
  
  RESULTS
  In total, 4413 patients were randomized; 3030 (1499 in the enoxaparin and 1531 in the semuloparin groups) were evaluable for the primary efficacy end point, which occurred in 97 patients (6.3%) in the semuloparin group and 82 patients (5.5%) in the enoxaparin group [odds ratio (OR) = 1.16, 95% confidence interval (CI): 0.84-1.59]. On the basis of a noninferiority margin of 1.25, postoperative semuloparin did not demonstrate noninferiority to preoperative enoxaparin. Major bleeding occurred in 63 of 2175 patients (2.9%) in the semuloparin group and 98 of 2177 patients (4.5%) in the enoxaparin group (OR = 0.63, 95% CI: 0.46-0.87).
  
  
  CONCLUSIONS
  Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery. Study registered with clinicaltrials.gov: NCT00679588.
authors.affiliation: *Thrombosis Research Institute and University College London, London, UK †Stroke Unit and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy ‡Department of Orthopaedic Surgery, McGill University Health Centre, Montreal, QC, Canada §Duke University Medical Center, Durham, NC ¶Spine Center Copenhagen, Copenhagen University Hospital, Glostrup, Denmark ‖University of Saint-Étienne, Saint-Étienne, France **Klinikum Frankfurt Höechst, Frankfurt, Germany ††Sanofi, Bridgewater, NJ ‡‡Hamilton Health Sciences General Hospital, McMaster University, Hamilton, ON, Canada.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Kakkar
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: William
authors.initials: W
authors.lastname: Fisher
authors.forename: Daniel
authors.initials: D
authors.lastname: George
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lassen
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.forename: Patrick
authors.initials: P
authors.lastname: Mouret
authors.forename: Judith
authors.initials: J
authors.lastname: Murphy
authors.forename: Francesca
authors.initials: F
authors.lastname: Lawson
authors.forename: Alexander G G
authors.initials: AG
authors.lastname: Turpie
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017984:Enoxaparin / Q000008:administration & dosage*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D005500:Follow-Up Studies; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D011184:Postoperative Period; D057234:Preoperative Period; D012189:Retrospective Studies; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; C569346:semuloparin