Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living, Interactive Systematic Review and Network Meta-analysis

Mayo Clin Proc. 2022 Feb;97(2):308-324. doi: 10.1016/j.mayocp.2020.10.041. Epub 2021 Jun 22.


Objective: To maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT).

Methods: We have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website

Results: The results are constantly updated as new information becomes available ( The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; I2, 25%) without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 to 2.18; I2, 28%). Mixed treatment comparisons show that apixaban (OR, 0.41; 95% credible interval [CrI], 0.16 to 0.95) and rivaroxaban (OR, 0.58; 95% CrI, 0.37 to 0.90) significantly decrease VTE recurrent events compared with dalteparin. Edoxaban significantly increases major bleeding compared with dalteparin (OR, 1.73; 95% CrI, 1.04 to 3.16), and rivaroxaban significantly increases clinically relevant nonmajor bleeding compared with dalteparin and other DOACs. There are no significant differences between DOACs in terms of VTE recurrences and major bleeding.

Conclusion: DOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs.

Registration: Open Science Framework (

Trial registration: NCT02744092 NCT02746185 NCT03139487 NCT02583191.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / therapeutic use*
  • Dalteparin / therapeutic use*
  • Hemorrhage / chemically induced
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Network Meta-Analysis
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / etiology


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Dalteparin

Associated data