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Clinical Studies

Low-molecular-weight heparin beyond 12 months in patients with cancer-associated thrombosis

Abstract

Background

Clinical guidelines indicate that in patients with cancer-associated thrombosis (CAT), anticoagulant treatment should be continued beyond 6 months as long as the cancer is active. We aimed to analyse the safety of low-molecular-weight heparin (LMWH) beyond 12 months in patients with CAT.

Methods

We performed a post hoc analysis of consecutive CAT patients from October 2008 to December 2019. The primary outcome was the rate of clinically relevant bleeding (CRB), and we compared two periods (1–12 vs. 12–24 months). Hazard ratio (HR), competing risk analysis and sensitivity analyses were performed.

Results

Of the 588 patients included, 30.1% (n = 177) received LMWH beyond 12 months. The rate of CRB in the first 12 months compared to the 12–24 month period was 3.2 per 100 patients/month (95% CI 2.5–4.1) vs. 0.9 per 100 patients/month (95% CI 0.4–1.5), (P < 0.0001). The competing risk analysis of CRB comparing both periods showed a lower sub-distribution hazard ratio (SHR) during the period 12–24 months (SHR: 0.5, 95% CI: 0.3–0.8, P < 0.001).

Conclusion

In patients with cancer-associated thrombosis under anticoagulant treatment with LMWH, the rate of clinically relevant bleeding and major bleeding were lower beyond 12 months.

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Data availability

The datasets generated and/or analysed during this study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Henry Antonio Andrade Ruiz, from the Methodological and Statistical Support Unit, for his support and contribution to the statistical analysis.

Funding

This project was supported by LEO Pharma Research Foundation.

Author information

Authors and Affiliations

Authors

Contributions

Conception and design: MB-H, SL-R, SM-R and LJ-P. Data analysis and interpretation: MB-H, SL-R, SM-R and LJ-P. Synthesis of the results: all authors. Manuscript writing: SL-R and LJ-P. Manuscripts review and edits. Final approval of manuscript: all authors. Accountable for all aspects of the work: all authors.

Corresponding author

Correspondence to Luis Jara-Palomares.

Ethics declarations

Competing interests

LJ-P reports personal fees from Bayer Hispania, Actelion, Rovi, Pfizer, Menarini, and Leo Pharma, outside the submitted work. ROC reports grant support from Leo Pharma and Bayer Healthcare, and fees for serving on advisory boards and giving lectures from Leo Pharma, Rovi, Bayer Healthcare, MSD and Actelion. There are no other competing interests.

Ethics approval and consent to participate

This post hoc analysis was evaluated and approved by the Ethical Committee of the centre according to Spanish Regulatory Authorities (0511-N-22). This study was conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Guidelines for Good Clinical Practice and in full conformity with relevant regulations. Documents constituting the master file of the study included all the documents established in good clinical practice (CPMP/ICH/135/95). In this project, the collection, process and analysis of all data were anonymously carried out, and only for the purposes of the project. All data were protected in accordance with the European Union directive 2016/679 of the European Parliament and the European Council, of April 27, 2016, regarding the protection of persons and their personal data.

Consent to publish

No publication consent is required for this specific study. This post hoc analysis was evaluated and approved by the Ethical Committee of the centre according to Spanish Regulatory Authorities (0511-N-22). Original prospective studies required informed consent.

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Lopez-Ruz, S., Barca-Hernando, M., Marin-Romero, S. et al. Low-molecular-weight heparin beyond 12 months in patients with cancer-associated thrombosis. Br J Cancer 127, 2234–2240 (2022). https://doi.org/10.1038/s41416-022-02007-x

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