title: Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation.
abstract: BACKGROUND
  Several basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patients with cancer through an antitumor effect in addition to their antithrombotic effect.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of oral anticoagulants in patients with cancer with no therapeutic or prophylactic indication for anticoagulation.
  
  
  METHODS
  We performed a comprehensive search for studies of anticoagulation in patients with cancer including 1. a February 2013 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE; 2. a handsearch of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with the 2003 issue); 3. checking of references of included studies; 4. use of the 'related citation' feature in PubMed; and 5. searching clinical trials.gov for ongoing studies.
  
  
  METHODS
  Randomized controlled trials (RCTs) comparing vitamin K antagonist or other oral anticoagulants with no intervention or placebo in patients with cancer without clinical evidence of venous thromboembolism.
  
  
  METHODS
  Using a standardized data form, we extracted data on risk of bias, participants, interventions and outcomes of interest that included all-cause mortality, venous thromboembolism, major bleeding, and minor bleeding.
  
  
  RESULTS
  Of 9559 identified citations, seven RCTs (eight reports) fulfilled the inclusion criteria. The oral anticoagulant was warfarin in six of these RCTs and apixaban in the seventh RCT. The comparator was either placebo or no intervention. The use of warfarin had no effect on mortality at six months (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.82 to 1.22), one year (RR 0.97; 95% CI 0.89 to 1.04), two years (RR 0.98; 95% CI 0.81 to 1.18), or five years (RR 0.92; 95% CI 0.83 to 1.01). One study assessed the effect of warfarin on venous thromboembolism and did not show or exclude a beneficial or detrimental of effect (RR 0.15; 95% CI 0.02 to 1.20). Warfarin increased both major bleeding (RR 4.24; 95% CI 1.86 to 9.65) and minor bleeding (RR 3.19; 95% CI 1.83 to 5.55). We judged the quality of evidence as moderate for all outcomes.The study assessing the effect of apixaban did not show or exclude a beneficial effect or detrimental of apixaban on mortality at six months (RR 0.16; 95% CI 0.01 to 1.66); major bleeding (RR 0.62; 95% CI 0.06 to 6.63); and minor bleeding (RR 2.87; 95% CI 0.16 to 51.82). We judged the quality of evidence as low for all outcomes.
  
  
  CONCLUSIONS
  Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer while the risk for bleeding is increased.
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: Irene
authors.initials: I
authors.lastname: Terrenato
authors.forename: Ignacio
authors.initials: I
authors.lastname: Neumann
authors.forename: Victor E D
authors.initials: VE
authors.lastname: Yosuico
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.forename: Francesca
authors.initials: F
authors.lastname: Sperati
authors.forename: Holger
authors.initials: H
authors.lastname: Schünemann
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000401:mortality; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality; D009369:Neoplasms / Q000401:mortality*; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D013923:Thromboembolism / Q000517:prevention & control; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin