Highlights
- Cancer-associated Venous Thromboembolism (VTE) significantly impacts morbidity and mortality in cancer patients.
- Direct Oral Anticoagulants (DOACs) have become the preferred treatment for cancer-associated VTE, offering advantages over traditional therapies.
- Special considerations are needed for patients with certain cancer types, renal dysfunction, or those with a high risk of bleeding.
- Recent studies suggest that reduced-dose anticoagulation therapy may be effective for extended treatment in some patients.
TLDR
This article reviews the evolving landscape of anticoagulation therapy for cancer-associated venous thrombosis (VTE), focusing on the use of Direct Oral Anticoagulants (DOACs), challenges in treating low thrombotic burden VTE, and strategies for optimizing therapy in patients with cancer.
Introduction
Venous Thromboembolism (VTE), which includes Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT), is a common and severe complication in cancer patients, accounting for around 20% of all VTE cases. With VTE being the second leading cause of death in cancer patients after cancer progression, it significantly affects morbidity and overall quality of life.
The introduction of Direct Oral Anticoagulants (DOACs) has revolutionized VTE treatment in recent years, offering convenience and efficacy over traditional anticoagulants like Low Molecular Weight Heparin (LMWH). However, managing VTE in cancer patients remains complex due to the risk of bleeding, especially in individuals with specific cancer types or those with other health complications. This review examines the latest evidence on the proper application of anticoagulation therapy for cancer-associated VTE and discusses emerging trends and challenges in treatment.
Treatment of Low Thrombotic Burden VTE in Cancer Patients
Advancements in diagnostic imaging have led to increased detection of cancer-associated VTE, even in asymptomatic patients. Studies indicate that up to 40-50% of pulmonary embolisms (PEs) in cancer patients are incidentally detected. Although standard guidelines recommend anticoagulation therapy for incidental PE, the management of low thrombotic burden VTE, such as subsegmental PE and isolated distal DVT, remains controversial.
Research suggests that anticoagulation therapy could be deferred in certain low-risk patients, such as those with isolated subsegmental PE and sufficient cardiopulmonary reserve. However, this conservative approach needs more evidence to be applied confidently to cancer patients. For instance, the risks associated with incidental subsegmental PE in cancer are comparable to more proximal PE, warranting therapeutic anticoagulation in many cases.
For patients with isolated distal DVT, the data indicate a significantly higher risk of VTE recurrence, major bleeding, and mortality compared to non-cancer-associated distal DVT. Therefore, anticoagulation therapy is recommended for these patients, as the risk of recurrent VTE in such cases is not negligible.
Optimal Choice and Dosage of Anticoagulants in Cancer-Associated VTE
Low Molecular Weight Heparin (LMWH) has been the standard treatment for cancer-associated VTE since the early 2000s. However, Direct Oral Anticoagulants (DOACs), which inhibit clotting factors such as factor Xa and thrombin, have gained popularity in recent years. DOACs offer several advantages over LMWH, including oral dosing, fixed dosing without the need for laboratory monitoring, and fewer drug-food interactions.
Despite these benefits, DOACs are not always suitable for all cancer patients. For instance, LMWH is recommended over DOACs for individuals with upper gastrointestinal or genitourinary cancers, or for patients on medications that interact with DOACs. Additionally, DOACs are not advised for patients with severe renal dysfunction (Creatinine Clearance < 30 mL/min), as most clinical trials have excluded this population.
New Developments in Anticoagulation Therapy
Emerging anticoagulants targeting Factor XI offer promising alternatives for managing cancer-associated VTE. Abelacimab, a monoclonal antibody targeting Factor XI, has gained attention due to its ability to minimize thrombosis without impacting hemostasis. With its long half-life and monthly dosing capability, Abelacimab offers a potentially more convenient option for cancer patients. Ongoing trials, such as the ASTER and MAGNOLIA studies, are evaluating the efficacy and safety of Abelacimab compared to DOACs and LMWH.
Optimal Duration of Anticoagulation Therapy in Cancer-Associated VTE
Determining the ideal duration of anticoagulation therapy is challenging, especially since the risk of VTE recurrence persists as long as cancer is active. Current guidelines recommend extended therapy beyond six months for patients with active cancer, as long as the bleeding risk is manageable.
The EVE trial compared reduced-dose apixaban with standard full-dose therapy during the extended treatment period, aiming to reduce bleeding risks without compromising anticoagulation efficacy. While the study did not show a statistically significant difference between the two groups, the reduced-dose therapy exhibited a slightly lower bleeding rate, indicating potential for reduced-dose options in the future.
Conclusion
The advent of Direct Oral Anticoagulants (DOACs) has revolutionized the management of cancer-associated venous thromboembolism (VTE). However, the treatment landscape continues to evolve, and further research is necessary to optimize the use of DOACs in diverse patient populations, particularly those at higher risk of bleeding or with specific cancer types.
Source: Yhim, H.-Y. (2024). Proper application of anticoagulation therapy on cancer-associated venous thrombosis. Blood Research, 59(25). https://doi.org/10.1007/s44313-024-00029-3