title: Prevention of venous thromboembolism in patients with immobilization of the lower extremities: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  It is controversial whether the prevention of venous thromboembolism (VTE) in patients with lower-leg immobilization is necessary.
  
  
  OBJECTIVE
  To assess the benefits and complications of pharmacological thromboprophylaxis, we performed a meta-analysis of all available randomized controlled trials on this subject.
  
  
  METHODS
  We searched the MEDLINE and EMBASE electronic databases. We included English- and non-English language studies, we hand-searched journals, and we contacted manufacturers. We analyzed data from six randomized trials that investigated pharmacological prophylaxis for the prevention of VTE in 1456 patients with lower-leg immobilization in plaster cast or orthosis. Two reviewers independently assessed the trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus or arbitrage.
  
  
  RESULTS
  The pooled estimate from all trials revealed a highly significant and clinically relevant reduction in asymptomatic events with low-molecular-weight heparin (LMWH) prophylaxis, compared to placebo or untreated control [risk ratio (RR) 0.58; 95% confidence interval (CI) 0.39-0.86; P = 0.006). The mean rate of VTE decreased from 17.1% to 9.6% with the use of LMWH. Subgroup analysis of methodologically superior trials (RR 0.68; CI 0.50-0.92; P = 0.01), proximal deep vein thrombosis (RR 0.28; CI 0.11-0.72; P = 0.008), tendon ruptures (RR 0.60; CI 0.38-0.97; P = 0.04), and fractures (RR 0.62; CI 0.45-0.86; P = 0.004) confirmed the robustness of the overall result. Frequency of bleeding did not differ between LMWH prophylaxis and control groups (RR 1.22; CI 0.61-2.46; P = 0.57).
  
  
  CONCLUSIONS
  Our findings indicate that thromboprophylaxis with LMWH for immobilization of the lower extremities reduces the risk of VTE. This benefit is achieved with no excess bleeding.
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: H B
authors.initials: HB
authors.lastname: Ettema
authors.forename: B J
authors.initials: BJ
authors.lastname: Kollen
authors.forename: C C P M
authors.initials: CC
authors.lastname: Verheyen
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D007103:Immobilization / Q000009:adverse effects*; D035002:Lower Extremity; D011292:Premedication; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight