Abstract

Cancer patients develop a hypercoagulable state with a four- to seven-fold higher thromboembolic risk compared to non-cancer patients. Thromboembolic events can precede the diagnosis of cancer, but they more often occur at diagnosis or during treatment. After malignancy itself, they represent the second cause of death. Low molecular weight heparins are the backbone of the treatment of cancer-associated thromboembolism. This treatment paradigm is possibly changing, as direct oral anticoagulants (DOACs) may prove to be an alternative therapeutic option. The currently available DOACs were approved during the first and second decades of the 21st century for various clinical indications. Three molecules (apixaban, edoxaban and rivaroxaban) are targeting the activated factor X and one (dabigatran) is directed against the activated factor II, thrombin. The major trials analyzed the effect of these agents in the general population, with only a small proportion of cancer patients. Two published and several ongoing studies are specifically investigating the use of DOACs in cancer-associated thromboembolism. This article will review the current available literature on the use of DOACs in cancer patients. Furthermore, we will discuss published data suggesting potential anti-cancer actions exerted by non-anticoagulant effects of DOACs. As soon as more prospective data becomes available, DOACs are likely to be considered as a potential new therapeutic option in the armamentarium for patients suffering of cancer-associated thromboembolism.

Highlights

  • Thromboembolism represents a common complication of cancer

  • According to some data about 25% of cancer patients are already treated with direct oral anticoagulants (DOACs) and 30% are under vitamin K antagonists (VKAs) [9]

  • Major bleeding occurred in this subgroup in 2.3% under apixaban and 5.0% under VKAs. These findings suggest that apixaban is effective as VKAs in preventing venous thromboembolic event (VTE)-recurrence without any significative difference in the safety profile

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Summary

Introduction

The risk of developing a venous thromboembolic event (VTE) associated with malignancy is estimated to be four to seven-fold higher compared to the normal population [1,2]. Treatments of the underlying neoplastic disease can be delayed, hospitalisation stay prolonged and, eventually, health-care costs are raised. All these characteristics highlight the importance of a well-managed treatment. Low-molecular-weight heparins (LMWHs) are the treatment of choice for TEs in cancer patients. Their utilization in daily practice is far from being ideal. According to some data about 25% of cancer patients are already treated with DOACs and 30% are under vitamin K antagonists (VKAs) [9]

Treatment of Cancer-Associated Venous Thromboembolism
General Aspects of DOACs and Concerns in Cancer Patients
Subgroup Analysis
Rivaroxaban
Edoxaban
Dabigatran
Apixaban
Meta-Analysis
Observational Studies
Concluded Prospective Studies
A Non-interventional Study on Xarelto for Treatment of Venous
Meta-Analysis of the Prospective Studies
Ongoing or in 2018 Concluded Clinical Trials
Anticancer Effect of Heparins
DOACs Beyond the Anticoagulation: A Potential Antineoplastic Effect?
Findings
Conclusions

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