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.

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 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.

Low-Molecular-Weight Heparin in Cancer Patients: Overview and Indications

2019 ◽  
Vol 39 (01) ◽  
pp. 067-075 ◽  
Author(s):  
Minna Voigtlaender ◽  
Florian Langer
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Anticancer Agents ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Vte Prophylaxis ◽  
Patients With Cancer ◽  
Increased Risk

AbstractAlthough venous thromboembolism (VTE) is a well-known cause of death in patients with cancer, both its treatment and prevention remain a challenge in daily practice. Direct oral anticoagulants have emerged as safe and efficacious alternatives to vitamin K antagonists in the general population, and recent clinical trials also support their use in select patients with cancer-associated VTE. Despite this, low-molecular-weight heparins (LMWHs), a comparatively ancient class of antithrombotic drugs, remain the anticoagulants of choice in many indications relevant to modern haematology and oncology. In addition to the treatment of established VTE, these indications include VTE prophylaxis in surgical or acutely ill, hospitalized medical cancer patients as well as the prevention of VTE in high-risk patients undergoing ambulatory chemotherapy. In a constantly changing landscape of approved anticancer agents, this review article summarizes pivotal clinical trial data and guideline recommendations regarding the use of LMWH in haematological and oncological patients, who constitute a highly vulnerable patient population due to their increased risk for both bleeding and VTE recurrence.

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.

scholarly journals Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment

2015 ◽  
Vol 22 (2) ◽  
pp. 144 ◽  
Author(s):  
J.C. Easaw ◽  
M.A. Shea-Budgell ◽  
C.M.J. Wu ◽  
P.M. Czaykowski ◽  
J. Kassis ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Renal Insufficiency ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Patients With Cancer ◽  
Clinical Scenarios ◽  
Increased Risk

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic.PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations.Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti–factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

scholarly journals Evaluation of Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in the Oncology Population

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5026-5026
Author(s):  
Jessica Hedvat ◽  
Christina Howlett ◽  
James K. McCloskey ◽  
Ruchi Jain
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Cancer Patients ◽  
Bleeding Episode ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Package Insert ◽  
Increased Risk ◽  
Clinically Significant ◽  
Risk For Bleeding

Abstract INTRODUCTION: Anticoagulant management of cancer-associated thrombosis is challenging since this patient population is concurrently at an increased risk for bleeding. The use of direct oral anticoagulants [(DOACs) dabigatran, rivaroxaban, apixaban] is not recommended for the treatment of venous thromboembolism (VTE) in cancer patients since there is limited data in this patient population. Despite limited evidence for use, DOACs are commonly prescribed due to ease of administration and lack of required laboratory monitoring. The objective of this study was to evaluate the practice and safety patterns of the DOACs when used for VTE treatment in the oncology population at Hackensack University Medical Center (HackensackUMC). METHODS: This study was a retrospective chart review of adult cancer patients treated at HackensackUMC who received dabigatran, rivaroxaban, or apixaban for the treatment of VTE. The protocol was reviewed and approved by the Institutional Review Board. Patients were identified through a computer generated report of the DOACs which included patients on all inpatient adult oncology floors at HackensackUMC from January 2013 to October 2015. Patients were included in this study if they were 18 years of age or older, admitted to an oncology floor, receiving a DOAC for VTE treatment for at least 48 hours, and had active cancer. Patients were excluded from this study if they were receiving hemodialysis or receiving a DOAC exclusively for the indication of atrial fibrillation. The primary outcomes of this study included the percentage of patients who were receiving a DOAC dosage consistent with that of the package insert and the percentage of patients who experienced clinically significant bleeding. The secondary outcomes of this study included the percentage of patients who had their DOAC held for thrombocytopenia and high risk procedures. Descriptive statistics were used to analyze study outcomes. RESULTS: Of the 126 patients screened, 39 patients were included. Thirty-five patients were on rivaroxaban and 4 patients were on apixaban (Table 1). Ten of 39 patients (26%) were not receiving a DOAC dosage consistent with that of the package insert. Of these 10 patients identified, the majority were receiving a lower DOAC dose than is recommended in the package insert. Our assumption is that these patients received a lower than recommended dose due to concerns for increased risk of bleeding. No patients experienced clinically significant bleeding. Four of 39 patients (10%) experienced a minor bleeding episode, all of which were gastrointestinal and/or genitourinary bleeds (Table 2). Four of 14 thrombocytopenic patients (29%) did not have their DOAC dose held for thrombocytopenia (none of which experienced a bleeding episode). All patients had their DOACs appropriately held for all procedures. CONCLUSION: Increased education and awareness on manufacturer recommended dosing of DOACs is warranted for oncology prescribers. Despite the increased risk for bleeding in cancer patients, no clinically significant bleeding events were identified in our patient cohort. To our knowledge, this is the first study to evaluate the use of DOACs for VTE treatment in patients with cancer at a high risk for bleeding. This data suggests that the use of DOACs may be safe to use for VTE treatment in the oncology population. This study may provide foundation for larger, randomized, controlled trials to determine whether DOACs should be used for VTE treatment in cancer patients. Disclosures Howlett: Eisai: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Sandoz: Honoraria; Teva: Speakers Bureau. McCloskey:Ariad: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau.

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 Primary Thromboprophylaxis in Patients with Malignancies: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO), the Society of Thrombosis and Hemostasis Research (GTH), and the Austrian Society of Hematology and Oncology (ÖGHO)

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2905
Author(s):  
Martin Kirschner ◽  
Nicole do Ó Hartmann ◽  
Stefani Parmentier ◽  
Christina Hart ◽  
Larissa Henze ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Working Party ◽  
Major Surgery ◽  
Thrombotic Risk ◽  
Indwelling Catheters ◽  
Increased Risk

Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles. After an episode of thrombosis in a cancer patient, secondary thromboprophylaxis to prevent recurrent thromboembolism has long been established and is typically continued as long as the cancer is active or actively treated. On the other hand, primary prophylaxis, even though firmly established in hospitalized cancer patients, has only recently been studied in ambulatory patients. This recent change is mostly due to the emergence of direct oral anticoagulants (DOACs). DOACs have a shorter half-life than vitamin K antagonists (VKA), and they overcome the need for parenteral application, the latter of which is associated with low-molecular-weight heparins (LMWH) and can be difficult for the patient to endure in the long term. Here, first, we discuss the clinical trials of primary thromboprophylaxis in the population of cancer patients in general, including the use of VKA, LMWH, and DOACs, and the potential drug interactions with pre-existing medications that need to be taken into account. Second, we focus on special situations in cancer patients where primary prophylactic anticoagulation should be considered, including myeloma, major surgery, indwelling catheters, or immobilization, concomitant diseases such as renal insufficiency, liver disease, or thrombophilia, as well as situations with a high bleeding risk, particularly thrombocytopenia, and specific drugs that may require primary thromboprophylaxis. We provide a novel algorithm intended to aid specialists but also family practitioners and nurses who care for cancer patients in the decision process of primary thromboprophylaxis in the individual patient.

scholarly journals Broadening the Categories of Patients Eligible for Extended Venous Thromboembolism Treatment

2019 ◽  
Vol 120 (01) ◽  
pp. 014-026 ◽  
Author(s):  
Marc Schindewolf ◽  
Jeffrey Ian Weitz
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Profile Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Specific Risk ◽  
Increased Risk

AbstractTraditionally, venous thromboembolism (VTE) resulting from major transient risk factors (e.g., surgery or trauma) or a major persistent risk factor such as cancer, has been defined as being provoked, whereas unprovoked VTE encompasses events without an identifiable cause. These categorizations influence anticoagulant treatment duration; unlike VTE provoked by major transient risk factors, extended anticoagulation beyond 3 months is advised for patients with cancer or unprovoked VTE due to risk persistence after treatment cessation. However, some patients with VTE provoked by minor transient or minor persistent risk factors may also be candidates for extended anticoagulation therapy due to the continuing risk of recurrence. In patients who require extended therapy, vitamin K antagonists (VKAs) are effective but are associated with an increased risk of bleeding and various treatment burdens (e.g., anticoagulation monitoring and dose adjustment). Evaluations of extended VTE treatment with the less-burdensome direct oral anticoagulants such as apixaban, dabigatran, edoxaban, and rivaroxaban show that they are at least as safe and effective as VKAs in a broad range of patients. In addition, apixaban and rivaroxaban offer more than one dosing option, allowing tailoring of treatment to the patient's specific risk factor profile. Analysis of more granular definitions for risk factor groupings has also yielded vital information on the most appropriate strategies for the treatment of patients with specific risk factors, highlighting that extended anticoagulation treatment may benefit those with minor transient and persistent environmental and nonenvironmental risk factors who commonly receive shorter-duration therapy.

Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER)

2019 ◽  
Vol 45 (08) ◽  
pp. 851-858 ◽  
Author(s):  
David Spirk ◽  
Tim Sebastian ◽  
Martin Banyai ◽  
Jürg H. Beer ◽  
Lucia Mazzolai ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Similar Rate ◽  
Increased Risk

AbstractRenal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41–3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57–2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41–2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14–0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17–2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.

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