title: Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer.
abstract: BACKGROUND
  Compared with patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.
  
  
  OBJECTIVE
  To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in patients with cancer.
  
  
  METHODS
  A comprehensive search for studies of anticoagulation in patients with cancer including a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science.
  
  
  METHODS
  Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in patients with cancer and objectively confirmed VTE.
  
  
  METHODS
  Using a standardized data form, review authors extracted data in duplicate on methodologic quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia.
  
  
  RESULTS
  Of 9559 identified citations, 16 RCTs were eligible: 13 compared LMWH with UFH, two compared fondaparinux with heparin, and one compared dalteparin with tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow-up with LMWH compared with UFH (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodologic quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of mortality (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63), or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin with tinzaparin found no statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).
  
  
  CONCLUSIONS
  LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review.
authors.affiliation: Department of Internal Medicine, American University of Beirut, Riad El Solh St, Beirut, Lebanon.
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: Lara
authors.initials: L
authors.lastname: Kahale
authors.forename: Ignacio
authors.initials: I
authors.lastname: Neumann
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.forename: Francesca
authors.initials: F
authors.lastname: Sperati
authors.forename: Irene
authors.initials: I
authors.lastname: Terrenato
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.forename: Holger
authors.initials: H
authors.lastname: Schünemann
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D017985:Dalteparin / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D000077425:Fondaparinux; D006493:Heparin / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000150:complications*; D011134:Polysaccharides / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D000078222:Tinzaparin; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D000078222:Tinzaparin; D006493:Heparin; D000077425:Fondaparinux; D017985:Dalteparin