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Research Article
1 May 2026

Comparative safety of direct oral anticoagulants and low-molecular-weight heparin in patients with venous thromboembolism and cancer in Europe

Authors: Ellen Brodin, Annie Young https://orcid.org/0000-0001-6611-6653, Florian Langer, Raza Alikhan https://orcid.org/0000-0001-8762-1149, Lauri Timo, Dimitra Lambrelli, Beth Nordstrom https://orcid.org/0000-0003-1743-9610, … Show All … , Alison Booth https://orcid.org/0000-0002-7977-9621, Sophie Graham https://orcid.org/0000-0002-7770-1863, Ruth Mokgokong, Aaron Jenkins https://orcid.org/0000-0001-9785-9388, Jose Chaves, Feng Dai, Rupesh Subash https://orcid.org/0009-0001-4940-225X, Moritz Lehne https://orcid.org/0000-0001-8435-1374, Marco Ghiani, Antje Mevius, Daniela Fliegner, and Anders Gottsäter https://orcid.org/0000-0003-0865-0000 [email protected]Author Info & Affiliations
Volume 15, Number 5
https://doi.org/10.57264/cer-2025-0072
PDFFormats

Abstract

Aim: This study aimed to compare the safety and effectiveness of direct oral anticoagulants (DOACs) with low-molecular-weight heparin (LMWH) in patients with venous thromboembolism (VTE) and active cancer in a real-world setting in Sweden, Norway, Finland, the UK and Germany. Materials & methods: This observational cohort study used datasets from Sweden, Norway, Finland (National Patient and Prescription Registers) the UK (Clinical Practice Research Datalink and Hospital Episode Statistics) and Germany (AOK Plus and GWQ) from 2013 to 2020. We identified treatment-naive adult patients with cancer-related VTE treated with a DOAC or LMWH. We employed inverse probability of treatment weighting for each DOAC-LMWH comparison and assessed recurrent VTE and bleeding risk (overall and by site: gastrointestinal [GI], intracranial hemorrhage [ICH] or other) within 6 months of treatment initiation. Fine–Gray models were fitted to estimate adjusted hazard ratios and country level estimates were meta-analyzed. Results: After inverse probability of treatment weighting, 30,002 and 2892 patients were included in the LMWH-apixaban comparison, and 29,976 and 4321 in the LMWH-rivaroxaban comparison, respectively. Recurrent VTE could not be assessed comparatively because of low numbers. At 6 months, apixaban was associated with a lower risk of overall and other (HR: 0.67 [95% CI: 0.53,0.86]; 0.64 [0.41,0.998]) bleeding compared with LMWH, with similar risks for GI and ICH bleeding (0.89 [0.61,1.29]; 0.67 [0.31,1.44], respectively). Rivaroxaban had a similar risk of overall, GI, and other bleeding (0.98 [0.83, 1.15]; 0.86 [0.47,1.58]; 0.89 [0.74,1.08]) compared with LMWH, but a lower risk of ICH (0.32 [0.13, 0.82]). Conclusion: These findings suggest that apixaban may offer a safer bleeding profile than LMWH for patients with cancer-associated VTE, particularly in reducing overall and other types of bleeding. Rivaroxaban also appears to be a viable alternative to LMWH, with a notably lower risk of ICH. These results provide valuable real-world insights in an area where evidence remains very limited and support the role of DOACs as a safe alternative to LMWH in patients with VTE and cancer.

Plain language summary

What was the aim of this research?

To compare the safety of blood thinners among patients with cancer and blood clots in Sweden, Norway, Finland, the UK and Germany.

How was the research carried out?

This study used data from Sweden, Finland, Norway, the UK and Germany between 2013 and 2020 from adults with cancer and blood clots who were prescribed either a direct oral anticoagulant (DOAC) or low-molecular-weight heparin (LMWH). Weighting methods were used to balance patient characteristics. We then compared the risk of bleeding within 6 months after starting treatment, combining results from different countries.

What were the results?

The study compared 30,002 patients taking LMWH with 2892 patients taking apixaban and also compared 29,976 patients taking LMWH with 4321 patients taking rivaroxaban. Patients taking apixaban showed an improved safety profile compared with LMWH for overall bleeding, whereas the overall bleeding risk was similar for rivaroxaban compared with LMWH.

What do the results of the study mean?

In patients with VTE and cancer, apixaban was associated with a lower risk of overall bleeding compared with LMWHs, whereas rivaroxaban had a similar risk of overall bleeding. This information can be used by doctors to help them choose the safest blood thinner for patients with cancer who have blood clots, potentially reducing the risk of dangerous bleeding complications.

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