title: Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.
abstract: BACKGROUND
  Venous thromboembolism (VTE) often complicates the clinical course of cancer disease. The risk is further increased by chemotherapy but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain.
  
  
  OBJECTIVE
  To assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy.
  
  
  METHODS
  The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 3 May 2011) and CENTRAL (2011, Issue 2). The authors searched clinical trials registries and reference lists of relevant studies.
  
  
  METHODS
  Randomised controlled trials (RCTs) comparing unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), direct thrombin inhibitors, direct factor Xa inhibitors or mechanical intervention to no intervention or placebo; or comparing two different anticoagulants.
  
  
  METHODS
  Data were extracted on methodological quality, patients, interventions and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively.
  
  
  RESULTS
  Nine RCTs with a total of 3538 patients were considered. None of the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical interventions. Overall, the risk of bias was low in most of the studies. LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.41 to 0.93) with no evidence of heterogeneity (I(2) = 0%). The number needed to treat to prevent a symptomatic VTE was 60. LMWH was associated with a 60% increase in major bleeding when compared with inactive control, although this was not statistically significant (RR 1.57, 95% CI 0.69 to 3.60; I(2) = 10%). There was a 45% reduction in overall VTE (RR 0.55, 95% CI 0.34 to 0.88; I(2) = 0%) while for symptomatic pulmonary embolism, asymptomatic VTE, minor bleeding and one-year mortality the differences between the LMWH and control groups were not statistically significant. The effect of the vitamin K antagonist warfarin on preventing symptomatic VTE, measured in only one study, was not statistically significant (RR 0.15, 95% CI 0.02 to 1.20). In one RCT of patients with myeloma, LMWH was associated with a 67% reduction in symptomatic VTE (RR 0.33, 95% CI 0.14 to 0.83) compared with warfarin, with no differences in major bleeding. Antithrombin, evaluated in one study on paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control.
  
  
  CONCLUSIONS
  Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. However, the lack of power hampers definite conclusions on the effects on major safety outcomes, which mandates additional studies to determine the risk to benefit ratio of LMWH in this setting.
authors.affiliation: Department of Medicine and Aging; Centre for Aging Sciences (Ce.S.I.), Internal Medicine Unit, “University G. D’Annunzio”Foundation, Chieti, Italy. mdinisio@unich.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Di Nisio
authors.forename: Ettore
authors.initials: E
authors.lastname: Porreca
authors.forename: Noemi
authors.initials: N
authors.lastname: Ferrante
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Otten
authors.forename: Franco
authors.initials: F
authors.lastname: Cuccurullo
authors.forename: Anne W S
authors.initials: AW
authors.lastname: Rutjes
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D000991:Antithrombins / Q000627:therapeutic use; D002648:Child; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D011655:Pulmonary Embolism / Q000209:etiology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D000991:Antithrombins; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin; D006493:Heparin