Treatment Patterns of Cancer-associated Thrombosis in the Netherlands: The Four Cities Study

Fleur H J Kaptein; Noori A M Guman; Susan B Lohle; Frederikus A Klok; Albert T A Mairuhu; Pieter W Kamphuisen; Nick Van Es; Menno V Huisman

doi:10.1055/a-2214-8101

Treatment Patterns of Cancer-associated Thrombosis in the Netherlands: The Four Cities Study

TH Open. 2024 Jan 30;8(1):e61-e71. doi: 10.1055/a-2214-8101. eCollection 2024 Jan.

Authors

Fleur H J Kaptein¹, Noori A M Guman^{2

3

4}, Susan B Lohle^{2

3}, Frederikus A Klok¹, Albert T A Mairuhu⁵, Pieter W Kamphuisen^{2

3

4}, Nick Van Es^{2

3}, Menno V Huisman¹

Affiliations

¹ Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
² Department of Vascular Medicine, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, the Netherlands.
³ Department of Pulmonary Hypertension and Thrombosis, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
⁴ Department of Internal Medicine, Tergooi Medical Center, Hilversum, the Netherlands.
⁵ Department of Internal Medicine, Haga Hospital, The Hague, the Netherlands.

Abstract

Background Current guidelines recommend either low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) as first-line treatment in cancer-associated venous thromboembolism (VTE). Aim This study aimed to investigate treatment regimens for cancer-associated VTE over the past 5 years, explore predictors for initial treatment (LMWH vs. DOAC), and to assess the risks of recurrent VTE and bleeding. Methods This was a Dutch, multicenter, retrospective cohort study including consecutive patients with cancer-associated VTE between 2017 and 2021. Treatment predictors were assessed with multivariable logistic regression models. Six-month cumulative incidences for recurrent VTE and major bleeding (MB) were estimated with death as competing risk. Results In total, 1,215 patients were included. The majority (1,134/1,192; 95%) started VTE treatment with anticoagulation: 561 LMWH (47%), 510 DOACs (43%), 27 vitamin K antagonist (2.3%), and 36 other/unknown type (3.0%). The proportion of patients primarily treated with DOACs increased from 18% (95% confidence interval [CI] 12-25) in 2017 to 70% (95% CI 62-78) in 2021. Poor performance status (adjusted odds ratio [aOR] 0.72, 95% CI 0.53-0.99) and distant metastases (aOR 0.61, 95% CI 0.45-0.82) were associated with primary treatment with LMWH. Total 6-month cumulative incidences were 6.0% (95% CI 4.8-7.5) for recurrent VTE and 7.0% (95% CI 5.7-8.6) for MB. During follow-up, 182 patients (15%) switched from LMWH to a DOAC, and 54 patients (4.4%) vice versa, for various reasons, including patient preference, recurrent thrombosis, and/or bleeding. Conclusion DOAC use in cancer-associated VTE has increased rapidly over the past years. Changes in anticoagulation regimen were frequent over time, and were often related to recurrent thrombotic and bleeding complications, illustrating the complexity and challenges of managing cancer-associated VTE.

Keywords: anticoagulants; cohort studies; hemorrhage; neoplasms; venous thromboembolism.

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).

Grants and funding

Funding The LUMC received independent financial support for part of salary costs of F.H.J.K. from Pfizer, Bayer Health Care, and LEO Pharma. F.A.K. has received research support from Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, VarmX, Daiichi Sankyo, Actelion, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation, and the Horizon Europe Program, all unrelated to this work and paid to his institution. M.V.H. has received research grants from Dutch Healthcare Fund, Dutch Heart Foundation, Bayer Health Care, Pfizer, BMS, Boehringer-Ingelheim, and LEO Pharma. P.W.K. has received research grants from Daiichi Sankyo and Roche Diagnostics and the Tergooi Academy, all transferred to his institute. N.v.E. reports advisory board honoraria from Daiichi Sankyo, Bayer, and LEO Pharma, which were transferred to his institute.