Physicians' Academy for Cardiovascular Education

DOACs versus LMWH for the treatment of cancer-associated thrombosis

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

Literature - Riaz I, Fuentes HE, Arsalan Ahmed Naqviet S et al. - Mayo Clin Proc. 2022 Feb;97(2):308-324. doi: 10.1016/j.mayocp.2020.10.041.

Introduction and methods

Background and aim of the study

The authors developed a novel, living, interactive systematic review and network meta-analysis which includes randomized controlled trials (RCTs) evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin (LMWH) in patients with cancer-associated thrombosis (CAT). The current article includes four RCTs, but results will be constantly be updated as results from new RCTs become available.


The current analysis included data from four RCTs (n=2894): Hokusai VTE (edoxaban vs. dalteparin) [1], SELECT-D (rivaroxaban vs. dalteparin) [2], ADAM VTE (apixaban vs. dalteparin) [3] and Caravaggio (apixaban vs. dalteparin) [4]. Caravaggio and Hokusai VTE included both patients with active cancer and a history of cancer, while SELECT-D and ADAM VTE only included patients with active cancer. The treatment duration in the Hokusai VTE trial was 6 to 12 months. In the other trials, the treatment duration was 6 months.

The efficacy and safety of DOACs compared with dalteparin were analyzed in a pairwise meta-analysis. A network meta-analysis was used to evaluate the comparative effectiveness and safety of different DOACs.


The primary efficacy outcome was recurrent VTE. Major safety outcomes included major bleeding and clinically relevant nonmajor bleeding. Other outcomes included net clinical benefit (composite of VTE and major bleeding), fatal bleeding and all-cause mortality.

Main results

DOACs versus dalteparin

Mixed treatment comparisons


DOACs decreased recurrent VTE events compared with dalteparin in patients with CAT. There was no difference between DOACs and dalteparin with regard to major bleedings. DOACs were associated with increased rates of clinically relevant nonmajor bleeding compared to dalteparin.

The authors wrote “The choice of DOACs is not an easy decision in the absence of direct clinical trial evidence. Both apixaban and rivaroxaban significantly reduce the risk of VTE recurrence compared with dalteparin. Both rivaroxaban and edoxaban appear to increase bleeding outcomes, which was not seen with apixaban.”


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Find this article online at Mayo Clin Proc. The living interactive results can be found here

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