scholarly journals Direct oral anticoagulants: now also for prevention and treatment of cancer-associated venous thromboembolism?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 136-143 ◽  
Author(s):  
Ingrid Pabinger ◽  
Julia Riedl
Keyword(s):  
Venous Thromboembolism ◽  
Primary Prevention ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Similar Efficacy ◽  
Prevention And Treatment ◽  
History Of ◽  
Meta Analyses

Abstract Data on specific studies in cancer patients using direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE) are still scarce. For preventing VTE with DOACs, current experience is still very limited, so definite conclusions cannot yet be drawn. However, DOACs have so far been compared with vitamin K antagonists (VKAs) in patients with acute VTE in 5 studies, and several hundreds of patients included in these studies had either active cancer, a history of cancer, or a new occurrence of cancer during the course of disease. Meta-analyses have revealed an at least similar efficacy and safety profile of DOACs compared with VKAs. A number of studies of cancer patients investigating primary prevention and treatment are underway, and some will be finalized soon. Nevertheless, we might need further trials, specifically on the prevention of VTE in patients who are at particularly high risk. This article also includes a personal opinion on the use of DOACs in cancer patients. In conclusion, the currently available data show that DOACs might be safe and efficacious in the treatment of VTE, however, this has yet to be proven in specifically designed trials in patients with cancer. With regard to prevention, thus far, even less data exist, and the outcomes of the ongoing studies have to be evaluated before DOACs may be used for primary prevention.

scholarly journals The Current Status of Direct Oral Anticoagulants in Cancer-Related Venous Thromboembolism Treatment

2020 ◽  
Vol 16 (2) ◽  
pp. 286-295
Author(s):  
К. V. Lobastov ◽  
I. V. Schastlivtsev
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Similar Efficacy ◽  
Current Status ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Discontinuation Of Treatment

This article is a review of epidemiology, pathogenesis and treatment of venous thromboembolism (VTE) in cancer patients. In accordance with actual guidelines, the duration of anticoagulant therapy of cancer-related venous thrombosis should be at least 6 months. The use of vitamin K antagonists (VKA) is associated with an increased risk of VTE recurrence and bleeding, so low molecular weight heparin (LMWH), in particular dalteparin, has been the "gold standard" until recently. Compared to VKA, prolonged use of LMWH can reduce the incidence of VTE recurrence without affecting the risk of bleeding or death. The main disadvantage of LMWH is low compliance, leading to premature discontinuation of treatment or switching to alternative anticoagulants. Direct oral anticoagulants (DOACs) have changed the situation. Compared to VKA, they demonstrated higher efficacy with a similar (or improved for individual DOACs) safety in patients with cancer-related VTE. Recently, the results of studies comparing the use of DOACs with dalteparin in cancer patients have been published: SELECT-D (rivaroxaban), HOKUSAI-VTE Cancer (edoxaban), ADAM VTE (apixaban), CARAVAGGIO (apixaban). Rivaroxaban showed higher efficacy than dalteparin with a similar risk of major bleeding, but an increased risk of clinically relevant non-major (CRNM) bleeding. Edoxaban had the same efficacy as dalteparin but increased risk of major but not CRNM bleeding. Apixaban showed similar efficacy and safety as dalteparin in the CARAVAGGIO study, but did not provide higher safety in the ADAM VTE study. It was noted that gastrointestinal and urogenital bleeding dominated in the structure of hemorrhagic complications of DOACs. The results of published trials are reflected in the current guidelines of the specialized societies. DOACs (particularly, rivaroxaban and edoxaban) are recommended for the VTE treatment in cancer patients.

First-Line Therapies for VTE Treatment and Secondary Prophylaxis in Patients With Cancer: A New Direction

2018 ◽  
Vol 33 (3) ◽  
pp. 356-363
Author(s):  
Samantha M. Vogel ◽  
Leticia V. Smith ◽  
Evan J. Peterson
Keyword(s):  
Venous Thromboembolism ◽  
English Language ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Secondary Prophylaxis ◽  
Careful Consideration ◽  
Patients With Cancer ◽  
Study Selection ◽  
Meta Analyses

Objective: To review evidence behind anticoagulants in cancer-associated venous thromboembolism (VTE) with a focus on low-molecular-weight heparins (LMWH) and the role of direct oral anticoagulants (DOACs). Data Sources: PubMed was searched using terms “venous thromboembolism,” “cancer,” and “anticoagulation.” This search was restricted to clinical trials, meta-analyses, and subgroup analyses. Additional references were identified from reviewing literature citations. Study Selection: English-language prospective and retrospective studies assessing the efficacy and safety of LMWH and DOACs in patients with cancer. Data Analysis: Several trials were analyzed that compared anticoagulation therapies for prevention of recurrent VTE in patients with cancer. Many studies comparing LMWH and vitamin K antagonists (VKAs) found nonsignificant differences between therapies. A single study demonstrated that LMWHs are superior to VKAs. This evidence supporting LMWH for long-term VTE treatment in patients with cancer is based on comparison to VKA, but results are limited by methodological issues, and the benefit of LMWH may be driven by poor control. Subanalyses of DOAC trials suggest these are equally or more effective as VKA in cancer, but this conclusion is underpowered. Conclusion: DOACs have the potential to bypass many challenges with traditional therapy. After analyzing the evidence available, we conclude that after careful consideration of risks and benefits, use of DOACs for VTE treatment are a reasonable option in patients with cancer.

Cancer-associated venous thromboembolism: Burden, mechanisms, and management

2017 ◽  
Vol 117 (02) ◽  
pp. 219-230 ◽  
Author(s):  
Cihan Ay ◽  
Ingrid Pabinger ◽  
Alexander T. Cohen
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Performance Status ◽  
Direct Oral Anticoagulants ◽  
Treatment Options ◽  
Cancer Site ◽  
Related Factors ◽  
Venous Diseases

SummaryVenous thromboembolism (VTE) is a significant health problem in the general population but especially in cancer patients. In this review, we discuss the epidemiology and burden of the disease, the pathophysiology of cancer-associated VTE, and the clinical treatment options for both primary prevention and acute treatment. Overall, the development of VTE in cancer patients is related to increases in morbidity, mortality, and medical costs. However, the incidence of cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia, comorbidities, performance status, history of venous diseases), tumour-related factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g. surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes) and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for the risk of VTE in cancer patients and have been used to enhance risk stratification. Evidence suggests that cancer itself is associated with a state of hypercoagulability, driven in part by the release of procoagulant factors, such as tissue factor, from malignant tissue as well as by inflammation-driven activation of endothelial cells, platelets, and leukocytes. In general, low-molecular-weight heparin (LWMH) monotherapy is the standard of care for the management of cancer-associated VTE, as vitamin K antagonists are less effective in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially promising treatment option for cancer patients with VTE, but recommendations concerning the routine use of DOACs should await head-to-head studies with LMWH.

Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism

Phlebologie ◽  
2017 ◽  
Vol 46 (06) ◽  
pp. 340-351
Author(s):  
M. Voigtlaender ◽  
F. Langer
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Phase ◽  
Standard Of Care ◽  
Longterm Treatment ◽  
Increased Risk ◽  
Direct Head

SummaryCancer patients with venous thromboembolism (VTE) are at increased risk for both bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin (LMWH) is the standard of care during the initial and longterm treatment phase (i.e. during the first 3–6 months of therapy) based on its overall beneficial safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are approved for the treatment of acute VTE, and the combined six phase-3 trials have included > 1 500 patients with active cancer, as defined by variable selection criteria. Subgroup analyses of these patients, either pooled or separately reported, suggest that DOACs could be a safe and efficacious alternative to VKA therapy for the treatment of cancer-associated VTE. However, the populations of cancer patients included in the DOAC and LMWH trials are not comparable with regard to mortality and VTE risk, and no specific data from direct head-to-head comparisons of DOACs with LMWHs are currently available. The use of DOACs for the management of VTE in cancer is thus not recommended by clinical practice guidelines.

scholarly journals Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials

Blood ◽  
2014 ◽  
Vol 124 (12) ◽  
pp. 1968-1975 ◽  
Author(s):  
Nick van Es ◽  
Michiel Coppens ◽  
Sam Schulman ◽  
Saskia Middeldorp ◽  
Harry R. Büller
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Similar Efficacy ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Key Points ◽  
Acute Venous Thromboembolism

Key Points DOACs have similar efficacy as VKAs in the treatment of acute symptomatic VTE, but significantly reduce the risk of major bleeding. The efficacy and safety of DOACs in the treatment of acute VTE are consistent in clinically important subgroups.

scholarly journals Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism

2017 ◽  
Vol 37 (04) ◽  
pp. 241-255 ◽  
Author(s):  
Minna Voigtlaender ◽  
Florian Langer
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Phase ◽  
Standard Of Care ◽  
Longterm Treatment ◽  
Increased Risk ◽  
Direct Head

SummaryCancer patients with venous thromboembolism (VTE) are at increased risk for both bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin (LMWH) is the standard of care during the initial and longterm treatment phase (i.e. during the first 3 – 6 months of therapy) based on its overall beneficial safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are approved for the treatment of acute VTE, and the combined six phase-3 trials have included > 1500 patients with active cancer, as defined by variable selection criteria. Subgroup analyses of these patients, either pooled or separately reported, suggest that DOACs could be a safe and efficacious alternative to VKA therapy for the treatment of cancer-associated VTE. However, the populations of cancer patients included in the DOAC and LMWH trials are not comparable with regard to mortality and VTE risk, and no specific data from direct head-to-head comparisons of DOACs with LMWHs are currently available. The use of DOACs for the management of VTE in cancer is thus not recommended by clinical practice guidelines.

scholarly journals Treatment Patterns and Clinical Outcomes in Korean Cancer Patients With Venous Thromboembolism: A Retrospective Cohort Study

2021 ◽  
Vol 27 ◽  
pp. 107602962097957
Author(s):  
Soo-Mee Bang ◽  
Jin-Hyoung Kang ◽  
Min Hee Hong ◽  
Jin-Seok Ahn ◽  
So Yeon Oh ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Events ◽  
Factors Associated ◽  
Vein Thrombosis ◽  
Medical Chart Review ◽  
Deep Vein

This study assessed epidemiologic data and clinical outcomes, including venous thromboembolism (VTE) recurrence and bleeding events, in patients with cancer-associated VTE, and assessed factors associated with clinical outcomes. Data were extracted from retrospective medical-chart review of adult patients diagnosed with cancer-associated deep vein thrombosis or pulmonary embolism who received anticoagulation treatment for ≥3 months. Patients were classified by: low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and other anticoagulants. First VTE recurrence and bleeding events, and factors associated with their occurrence, were assessed during the initial 6 months of treatment. Overall, 623 patients (age: 63.7 ± 11.3 years, 49.3% male) were included (119, 132, and 372 patients in LMWH, DOACs and other anticoagulants groups, respectively). The cumulative 6-month incidence of VTE recurrence was 16.6% (total), 8.3% (LMWH), 16.7% (DOACs), and 20.7% (other); respective bleeding events were 22.5%, 11.0%, 12.3%, and 30.7%). VTE recurrence and bleeding rates differed only between LMWH and other anticoagulants (HR 2.4, 95% CI: 1.2-5.0 and 3.6, 1.9-6.8, respectively). These results highlight the importance of initial VTE treatment choice for preventing VTE recurrence and bleeding events. LMWH or DOACs for ≥3 months can be considered for effective VTE management in cancer patients.

scholarly journals Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Ali Zalpour ◽  
Thein Hlaing Oo
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Current Evidence ◽  
Thrombin Inhibitor ◽  
Prevention And Treatment ◽  
Financial Impacts

Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed.

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