Treatment of venous thromboembolism in patients with cancer: A network meta-analysis comparing efficacy and safety of anticoagulants

Thromb Res. 2015 Sep;136(3):582-9. doi: 10.1016/j.thromres.2015.07.011. Epub 2015 Jul 17.


Introduction: Low-molecular-weight heparin (LMWH) and vitamin K antagonists (VKA) are current treatment options for cancer patients suffering from acute venous thromboembolism (VTE). The role of direct-acting oral anticoagulants (DOACs) for the treatment of VTE in cancer patients, particular in comparison with the current standard of care which is LMWH, remains unclear. In this network meta-analysis, we compared the relative efficacy and safety of LMWH, VKA, and DOAC for the treatment of cancer-associated VTE.

Methods: A pre-specified search protocol identified 10 randomized controlled trials including 3242 cancer patients. Relative risks (RR) of recurrent VTE (efficacy) and major bleeding (safety) were analyzed using a random-effects meta-regression model.

Results: LMWH emerged as significantly superior to VKA with respect to risk reduction of recurrent VTE (RR=0.60, 95%CI:0.45-0.79, p<0.001), and its safety was comparable to VKA (RR=1.08, 95%CI:0.70-1.66, p=0.74). For the DOAC vs. VKA efficacy and safety comparison, the relative risk estimates were in favor of DOAC, but had confidence intervals that still included equivalence (RR for recurrent VTE=0.65, 95%CI:0.38-1.09, p=0.10; RR for major bleeding=0.72, 95%CI:0.39-1.37, p=0.32). In the indirect network comparison between DOAC and LMWH, the results indicated comparable efficacy (RR=1.08, 95%CI:0.59-1.95, p=0.81), and a non-significant relative risk towards improved safety with DOAC (RR=0.67, 95%CI:0.31-1.46, p=0.31). The results prevailed after adjusting for different risk of recurrent VTE and major bleeding between LMWH vs. VKA and DOAC vs. VKA studies.

Conclusion: The efficacy and safety of LMWH and DOACs for the treatment of VTE in cancer patients may be comparable.

Funding: Austrian Science Fund (FWF-SFB-54).

Keywords: Cancer; Low-molecular-weight-heparin; Network meta analysis; Oral anticoagulants; Treatment; Venous thromboembolism.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticoagulants / adverse effects
  • Anticoagulants / classification
  • Anticoagulants / therapeutic use*
  • Causality
  • Comorbidity
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Evidence-Based Medicine
  • Female
  • Hemorrhage / epidemiology*
  • Hemorrhage / etiology
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / adverse effects
  • Humans
  • Incidence
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology*
  • Risk Assessment
  • Treatment Outcome
  • Venous Thromboembolism / epidemiology*
  • Venous Thromboembolism / prevention & control*
  • Vitamin K / antagonists & inhibitors


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Vitamin K