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 Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis

2015 ◽  
Vol 22 (2) ◽  
pp. 133 ◽  
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 ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Patients With Cancer ◽  
Clinical Scenarios ◽  
Increased Risk ◽  
Prophylactic Anticoagulation

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of 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 can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.

scholarly journals Recent advances in the treatment and prevention of venous thromboembolism in cancer patients: role of the direct oral anticoagulants and their unique challenges

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 974 ◽  
Author(s):  
Dominique Farge ◽  
Corinne Frere
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Patient Characteristics ◽  
Primary Prophylaxis ◽  
Disease Stage ◽  
Vte Prophylaxis ◽  
Patients With Cancer ◽  
Increased Risk

Venous thromboembolism (VTE) is a common complication in patients with cancer and is associated with poor prognosis. Low-molecular-weight heparins (LMWHs) are the standard of care for the treatment of cancer-associated thrombosis. Primary VTE prophylaxis with LMWH is recommended after cancer surgery and in hospitalized patients with reduced mobility. However, owing to wide variations in VTE and bleeding risk, based on disease stage, anti-cancer treatments, and individual patient characteristics, routine primary prophylaxis is not recommended in ambulatory cancer patients undergoing chemotherapy. Efforts are under way to validate risk assessment models that will help identify those patients in whom the benefits of primary prophylaxis will outweigh the risks. In recent months, long-awaited dedicated clinical trials assessing the direct oral anticoagulants (DOACs) in patients with cancer have reported promising results. In comparison with the LMWHs, the DOACs were reported to be non-inferior to prevent VTE recurrence. However, there was an increased risk of bleeding, particularly in gastrointestinal cancers. Safe and optimal treatment with the DOACs in the patient with cancer will require vigilant patient selection based on patient characteristics, co-morbidities, and the potential for drug–drug interactions.

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.

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

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.

Direct oral factor Xa inhibitors for the treatment of acute cancer-associated venous thromboembolism: A systematic review and network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Indirect Comparison ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Efficacy And Safety ◽  
Patients With Cancer

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.

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 Accredited Interactive Web-Based Application for the 2016 International Clinical Practice Guidelines on Thrombosis in Cancer: Improving Knowledge Transfer in Daily Clinical Practice

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5954-5954
Author(s):  
Dominique Farge
Keyword(s):  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Web Based ◽  
Patients With Cancer ◽  
The Impact

Abstract Venous thromboembolism (VTE) is a major therapeutic concern in cancer patients and the leading cause of death after metastasis. Providing anticoagulant therapy to this patient population is challenging because cancer patients are at increased risk of VTE recurrence and bleeding, and treatment management is often complicated by other co-morbidities that affect choice of anticoagulation. The International Initiative on Thrombosis and Cancer (ITAC-CME) is a multidisciplinary group of International academic clinicians, researchers, and experts dedicated to reducing the global burden of VTE and its consequences in cancer patients. In 2013, the group published international clinical practice guidelines for the treatment and prophylaxis of VTE in cancer (1, 2). In collaboration with CME solutions, an accredited CME provider, ITAC-CME developed a mobile web-based application to promote the international implementation of the 2013 guidelines, in English and French (www.itacc-cme.org). Usage of the app has steadily increased every year since its release. ITAC-CME recently revised its consensus recommendations according to a systematic review of the literature up to January 2016. In particular, the ISTH-endorsed updated recommendations provide a guidance on the use of the direct oral anticoagulants based on the current level of evidence (3). ITAC-CME and CME solutions have updated the web-based application to support the 2016 guidelines. The app also includes several new features, including interactive case-based CME learning activities, with pre- and post-activity practice assessments. These pre- and post-test metrics will be documented to record international clinical practice patterns, and monitor the impact of the app on the adoption of the 2016 guidelines into clinical practice worldwide. Translation of the 2016 updated app into additional languages is planned. The application has been submitted for accreditation with the royal College of Physicians and surgeons of Canada, the American Medical Association, the European Union of Medical Specialists, l' Organisme Gestionnaire du Développement Professionnel Continu, and the European Board for Accreditation in Hematology. 1 Debourdeau P, Farge D, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Büller HR, Bounameaux H. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. J Thromb Haemost. 2013 Jan;11(1):71-80. 2 Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Büller HR. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.J Thromb Haemost. 2013 Jan;11(1):56-70 3 Farge D, Bounameaux H , Brenner B, Cajfinger F, Debourdeau P, Khorana AA, Pabinger I, Solymoss S, Douketis J, Kakkar A. 2016 International Clinical Practice Guidelines Including Guidance for the Direct Oral Anticoagulants in the Treatment and Prophylaxis of Venous Thromboembolism in Patients With Cancer. Lancet Onccology 2016 (in press) Disclosures No relevant conflicts of interest to declare.

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 Prevention and treatment of cancer-associated thrombosis

2020 ◽  
Vol 27 (5) ◽  
Author(s):  
S. Ng ◽  
M. Carrier
Keyword(s):  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Standard Of Care ◽  
Low Molecular Weight ◽  
Safe Alternative ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Cancer Associated Thrombosis

Cancer is a hypercoagulable state with an associated increased risk of venous thromboembolism (vte) that is further amplified in individuals who undergo chemotherapy. Compared with patients having cancer alone or vte alone, patients who develop cancer-associated vte have a significantly poorer prognosis. The risks of recurrent vte despite appropriate anticoagulation therapy and of bleeding are also higher in patients with cancer than in those without. For those reasons, the prevention and appropriate management of cancer-associated thrombosis is of paramount importance. Although low-molecular-weight heparin has been the standard of care for the prevention and treat­ment of cancer-associated thrombosis, direct oral anticoagulants are increasingly being adopted as an effective and safe alternative.

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