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

**Authors:** 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

PMC · DOI: 10.1055/a-2214-8101 · TH Open: Companion Journal to Thrombosis and Haemostasis · 2024-01-30

## TL;DR

This study analyzed how cancer patients in the Netherlands are treated for blood clots, finding that the use of DOACs has increased significantly over five years.

## Contribution

The study provides updated insights into treatment trends and outcomes for cancer-associated thrombosis in a real-world setting.

## Key findings

- DOACs became the primary treatment for 70% of patients by 2021, up from 18% in 2017.
- Patients with poor performance status or distant metastases were more likely to receive LMWH.
- About 15% of patients switched from LMWH to DOACs during follow-up due to complications.

## 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.

## Linked entities

- **Diseases:** cancer (MONDO:0004992), venous thromboembolism (MONDO:0005399)

## Full-text entities

- **Genes:** ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) [NCBI Gene 6098] {aka MCF3, ROS, c-ros-1}
- **Diseases:** hematuria (MESH:D006417), renal dysfunction (MESH:D007674), lung cancer (MESH:D008175), stroke (MESH:D020521), ischemic strokes (MESH:D002544), prostate cancer (MESH:D011471), esophagus, stomach (MESH:D013272), renal vein thrombosis (MESH:D012170), Hepatobiliary cancer (MESH:D009369), bleeding complications (MESH:D008107), intracranial bleeding (MESH:D013345), VTE (MESH:D054556), ischemic attack (MESH:D002546), hematologic malignancies (MESH:D019337), nonsmall-cell lung cancer (MESH:D002289), anemia (MESH:D000740), Cardiovascular disease (MESH:D002318), death (MESH:D003643), atrial fibrillation (MESH:D001281), MBs (MESH:C567291), Chronic obstructive pulmonary disease (MESH:D029424), nonmelanoma skin cancer (MESH:D012878), ATE (MESH:D013923), aortic aneurysm (MESH:D001014), Upper gastrointestinal cancers (MESH:D005770), myocardial infarction (MESH:D009203), DVT (MESH:D020246), colon carcinoma (MESH:D003110), MB (MESH:D004830), colorectal or genitourinary cancer (MESH:D015179), pulmonary embolism (MESH:D011655), epistaxis (MESH:D004844), peripheral arterial occlusion (MESH:C564658), inferior vena cava thrombosis (MESH:C563013), coronary artery disease (MESH:D003324), PEs (MESH:D005413), Bleeding (MESH:D006470), gastrointestinal and genitourinary tumors (MESH:D014565), metastases (MESH:D009362), portal, hepatic, splenic, and mesenteric) vein thrombosis (MESH:D006502), gastrointestinal (MESH:D005767), Thrombosis (MESH:D013927), cerebral vein thrombosis (MESH:D020767), heart failure (MESH:D006333)
- **Chemicals:** LMWH (MESH:D006495), dabigatran (MESH:D000069604), DOAC (-), heparin (MESH:D006493), edoxaban (MESH:C552171), platinum (MESH:D010984)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10827569/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC10827569/full.md

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Source: https://tomesphere.com/paper/PMC10827569