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.

Treatment and secondary prevention of venous thrombo -embolism in cancer patients

2012 ◽  
Vol 32 (02) ◽  
pp. 139-144 ◽  
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Initial Period ◽  
Factor Xa ◽  
Secondary Prophylaxis ◽  
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 cancer-associated 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 anti-coagulants 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 also in cancer patients. 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.

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.

Abstract 301: Evaluation Of Net Clinical Benefits Of New Oral Anticoagulants Used For Acute Venous Thromboembolism Treatment vs. Standard Therapy

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Alpesh Amin ◽  
Yonghua Jing ◽  
Jeffrey Trocio ◽  
Jay Lin ◽  
Melissa Lingohr-Smith ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Standard Therapy ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Primary Efficacy ◽  
Clinical Benefits ◽  
Recurrent Vte ◽  
Event Rates

Background: Venous thromboembolism (VTE) is a significant healthcare burden, but is a preventable and treatable condition. The new oral anticoagulants (NOACs), apixaban, rivaroxaban, dabigatran, and edoxaban have all been shown in phase III trials to be noninferior in efficacy to standard therapies for acute VTE treatment, although there may be some differences in the bleeding rates among the NOACs. This study evaluated the net clinical benefits (NCB) of NOACs vs. standard therapies based on the AMPLIFY, EINSTEIN-Pooled analysis, RECOVER-1, RE-COVER II, and Hokusai-VTE trial results. Methods: Event rates of the primary efficacy and safety outcomes, as defined in each original trial, among VTE patients during trial periods were obtained from the published clinical trial data. Data from RECOVER-I and -II trials were combined to represent the findings for dabigatran since the two trials were of similar design. EINSTEIN-pooled (DVT and PE combined) data were used to represent findings for rivaroxaban. The combinations of rates for the primary efficacy endpoint, representing recurrent VTE or death and major bleedings (MB) were evaluated and defined as the NCB of each NOAC. Additionally, the number of VTE patients needed to treat (NNT) to avoid one event (e.g. VTE or MB) with each NOAC was also determined. Results: For patients treated in the VTE clinical trials, the differences in event rates of recurrent VTE or death for apixaban, rivaroxaban, dabigatran, and edoxaban vs. standard therapy were -0.43%, -0.23%, 0.20%, and -0.34%, respectively. The differences in event rates of MB for apixaban, rivaroxaban, dabigatran, and edoxaban vs. standard therapy were -1.26%, -0.78%, -0.43%, and -0.24%, respectively. The NCB improved for all NOAC treated patients, with those treated with apixaban (-1.69%) vs. standard therapy having the greatest NCB, followed by those treated with rivaroxaban (-1.01%), edoxaban (-0.58%), and dabigatran ( -0.23%) (Table 1). Conclusions: All NOACs were shown to be non-inferior to standard VTE treatments in clinical trials; however, apixaban may provide the optimal NCB with the lowest NNT. How these results translate into real-world outcomes or medical cost reductions will require further evaluation.

Spotlight on advances in VTE management: CALLISTO and EINSTEIN CHOICE

2016 ◽  
Vol 116 (S 02) ◽  
pp. S24-S32 ◽  
Author(s):  
Miriam Bach ◽  
Rupert Bauersachs
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Research Programme ◽  
Phase Iii ◽  
Current Evidence ◽  
Thromboembolism Prophylaxis ◽  
Patients With Cancer ◽  
Patient Reported ◽  
Cancer Associated Thrombosis

SummaryVenous thromboembolism (VTE) is associated with numerous complications and high mortality rates. Patients with cancer are at high risk of developing cancer-associated thrombosis (CAT), and VTE recurrence is common. Evidence supporting use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in patients with cancer is lacking – direct comparisons between NOACs and low-molecular-weight heparin (LMWH) are needed, along with patient-reported outcomes. Cancer Associated thrombosis – expLoring soLutions for patients through Treatment and Prevention with RivarOxaban (CALLISTO) is an international research programme exploring the potential of the direct, oral factor Xa inhibitor rivaroxaban for the prevention and treatment of CAT, supplementing existing data from EINSTEIN DVT and EINSTEIN PE. Here, we focus on four CALLISTO studies: A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous Thromboembolism Prophylaxis in Ambulatory Cancer Participants receiving Chemotherapy (CASSINI), Antico-agulation Therapy in SELECTeD Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT-D), Rivaroxaban in the Treatment of Venous Thromboembolism in Cancer Patients – a Randomized Phase III Study (CONKO-011) and a database analysis. Optimal anticoagulation duration for VTE treatment has always been unclear. Following favourable results for rivaroxaban 20 mg once-daily (Q. D.) for secondary VTE prevention (EINSTEIN EXT), EINSTEIN CHOICE is assessing rivaroxaban safety and (20 mg Q. D. or 10 mg Q. D.) vs acetylsalicylic acid (ASA), and will investigate whether an alternative rivaroxaban dose (10 mg Q. D.) could offer long-term VTE protection. It is anticipated that results from these studies will provide important answers and expand upon current evidence for rivaroxaban in VTE management.

scholarly journals Efficacy and safety of new oral anticoagulants in prophylaxis and treatment of venous thromboembolism

2010 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
Luca Masotti
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Clinical Development ◽  
Ease Of Use ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Thrombin Inhibitors ◽  
Phase Iii Clinical Trials ◽  
Phase Iii Trials

One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievementof these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. Dabigatran (anti-factor IIa), rivaroxaban, and apixaban (anti-Xa) are in advanced phase of clinical development with concluded phase III trials. Up to now the results of efficacy and safetyof phase III clinical trials are available, while phase IV studies are currently ongoing. Overall, the phase III clinical trials showed the non inferiority of new oral anticoagulants in VTE prophylaxis of patients undergone to major orthopedic surgery, such as hip and knee arthroplasty, compared toconventional prophylaxis represented by subcutaneous low molecular weight heparin with similar safety. Moreover dabigatran has shown to be not inferior when compared to warfarin for the prevention of six months VTE recurrences, with a significative lower incidence of bleedings. Awaitingthe results of many other ongoing phase III trials, since now it is possible to think that, in the next future, new oral anticoagulants will be widely diffused in clinical practice for their ease of use and feasibility. In this review the Authors analyse the available results of phase III clinical trials for dabigatran, rivaroxaban and apixaban, focusing on the antithrombotic endpoints for prevention andtreatment of VTE and the bleeding risk. Moreover synthesis of ongoing trials will be displayed.

scholarly journals Efficacy and safety of new oral anticoagulants in prophylaxis and treatment of venous thromboembolism

2010 ◽  
Vol 1 (1) ◽  
pp. 7-26 ◽  
Author(s):  
Luca Masotti ◽  
Cecilia Becattini ◽  
Roberto Cappelli ◽  
Giancarlo Landini ◽  
Alessandro Pampana ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Clinical Development ◽  
Ease Of Use ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Phase Iii Clinical Trials ◽  
Phase Iii Trials

One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievement of these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. Dabigatran (anti-factor IIa), rivaroxaban, and apixaban (anti-Xa) are in advanced phase of clinical development with concluded phase III trials. Up to now the results of efficacy and safety of phase III clinical trials are available, while phase IV studies are currently ongoing. Overall, the phase III clinical trials showed the non inferiority of new oral anticoagulants in VTE prophylaxis of patients undergone to major orthopedic surgery, such as hip and knee arthroplasty, compared to conventional prophylaxis represented by subcutaneous low molecular weight heparin with similar safety. Moreover dabigatran has shown to be not inferior when compared to warfarin for the prevention of six months VTE recurrences, with a significative lower incidence of bleedings. Awaiting the results of many other ongoing phase III trials, since now it is possible to think that, in the next future, new oral anticoagulants will be widely diffused in clinical practice for their ease of use and feasibility. In this review the Authors analyse the available results of phase III clinical trials for dabigatran, rivaroxaban and apixaban, focusing on the antithrombotic endpoints for prevention and treatment of VTE and the bleeding risk. Moreover synthesis of ongoing trials will be displayed.

How I treat venous thromboembolism in patients with cancer

Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4027-4033 ◽  
Author(s):  
Paolo Prandoni
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Outpatient Setting ◽  
Bleeding Complications ◽  
Fixed Dose ◽  
Patients With Cancer ◽  
Term Administration ◽  
Adjusted Dose

Venous thromboembolism (VTE) is a frequent complication in cancer patients and represents an important cause of morbidity and mortality. Especially in patients who have a poor life expectancy, preventing death from pulmonary embolism is the mainstay of treatment. Critically ill patients should promptly be administered thrombolytic drugs. Except for selected patients requiring aggressive therapy, the initial VTE treatment should be conducted with either adjusted-dose unfractionated heparin or fixed-dose low-molecular-weight heparin (LMWH). LMWHs have the potential to greatly simplify the initial treatment of VTE, making the treatment of suitable patients feasible in an outpatient setting. During anticoagulant therapy, cancer patients have a 2- to 4-fold higher risk of recurrent VTE and major bleeding complications when compared with noncancer patients. The long-term administration of LMWH should be considered as an alternative to anti-vitamin K drugs in patients with advanced disease and in those with conditions limiting the use of oral anticoagulants. Prolongation of anticoagulation should be considered for as long as the malignant disorder is active. The evidence of lowered cancer mortality in patients on LMWH has stimulated renewed interest in these agents as antineoplastic drugs and raises the distinct possibility that cancer and thrombosis share common mechanisms.

scholarly journals Treatment Challenges in Venous Thromboembolism: An Appraisal of Rivaroxaban Studies

2018 ◽  
Vol 118 (S 01) ◽  
pp. S23-S33 ◽  
Author(s):  
Jeffrey Weitz ◽  
Alok Khorana
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Phase Iii ◽  
Double Blind ◽  
Patients With Cancer ◽  
Patient Profile ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis

AbstractVenous thromboembolism (VTE) presents a continuing clinical burden to healthcare systems and there are patient groups for whom VTE management is challenging. Depending on the patient profile, the optimal duration of anticoagulation for VTE treatment can be unclear. EINSTEIN CHOICE was a Phase III, randomized, double-blind trial that compared the safety and efficacy of two once-daily (od) doses of the direct, oral factor Xa inhibitor rivaroxaban (20 and 10 mg) with acetylsalicylic acid (ASA; 100 mg daily) for prevention of recurrent VTE. Extended therapy with rivaroxaban at either dose was more effective than ASA at preventing recurrent VTE without increasing bleeding risk. Another group that is challenging to treat in the context of VTE is patients with cancer-associated thrombosis. Cancer is associated with a hypercoagulable state, while cancer treatment itself may increase VTE risk. Evidence supporting the use of non-vitamin K antagonist oral anticoagulants in patients with cancer is growing through specifically designed studies. Cancer Associated thrombosis—expLoring soLutions for patIentS through Treatment and prevention with rivarOxaban (CALLISTO) is an international research program exploring the role of rivaroxaban for the prevention and treatment of cancer-associated thrombosis. Here, we present overviews of three CALLISTO studies: PRO-LAPS II, CASTA-DIVA and COSIMO. Currently available and anticipated results from studies in a variety of patients at risk of or with VTE will provide valuable insights and seek to optimize future VTE management.

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 Success of Online CME at Improving Knowledge and Confidence Around Guideline-Directed Management of Cancer-Associated Thrombosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Caroline Padbury ◽  
Margaret Harris ◽  
Michael LaCouture ◽  
Jelena Spyropoulos
Keyword(s):  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Treatment Guidelines ◽  
Conflicts Of Interest ◽  
Oral Anticoagulants ◽  
Roundtable Discussion ◽  
Patients With Cancer ◽  
Cancer Associated Thrombosis ◽  
Post Assessment

Title:Success of Online CME at Improving Knowledge and Confidence Around Guideline-Directed Management of Cancer-Associated Thrombosis Study Objectives:Recent guidance statements recommend the use of direct oral anticoagulants (DOACs) as primary thromboprophylaxis in ambulatory patients with cancer who are starting chemotherapy and in patients with cancer and acute venous thromboembolism at low risk of bleeding and no drug-drug interactions.[Farge 2019; Key 2020] Yet, many clinicians lack knowledge and confidence with integrating DOACs into management strategies for patients with cancer in accordance to guideline recommendations.[Cushman 2015; Khorana 2016] We sought to determine if online continuing medical education (CME) could improve the knowledge and confidence of hematologists/oncologists regarding guideline-directed use of DOACs in the management of cancer-associated thrombosis. Methods:This CME intervention comprised of a 30-minute online video-based roundtable discussion among experts in the field of cancer-associated thrombosis management. Responses to 3 multiple-choice, knowledge questions and 1 self-efficacy, 5-point Likert scale confidence question were analyzed using a repeated pairs pre-/post-assessment study design. A chi-square test (P <.05 is considered significant) assessed pre- to post-activity change . The activity launched December 23, 2019, and data were collected through February 24, 2020. Results:In total, 71 Hematologists/Oncologists were included in this study. Overall, there were knowledge and confidence improvements seen among all groups from pre- to post-assessment: 27% of hematologists/oncologists (P<.01) improved at identifying guideline-directed therapy regarding recommended thromboprophylaxis in patients with cancer per guideline recommendations.27% of hematologists/oncologists (P<.01) improved at selecting guideline-appropriate treatment options for cancer-associated thrombosis.44% of hematologists/oncologists had an increase in confidence in managing thrombosis in patients with cancer. Continued educational gaps: 25% of hematologists/oncologists failed to select guideline recommended DOAC therapy for thromboprophylaxis in cancer patients.45% of hematologists/oncologists failed to select guideline recommended DOAC therapy for treatment of thrombosis in cancer patients.66% of hematologists/oncologists still remain at only a rating of 1 to 3 on a scale of 1 to 5 in their confidence managing thrombosis in patients with cancer. Conclusion:This study demonstrates the success of online, CME-accredited, video-based roundtable discussion with experts in the field on significantly improving knowledge and confidence of hematologists/oncologists related to the guideline-recommended use of DOACs in the management of cancer-associated thrombosis. Continued gaps were also identified for future educational targets. Sources of support: Developed through an independent educational grant from Janssen in partnership with the University of Chicago. References: Cushman M, Creager MA. Improving awareness and outcomes related to venous thromboembolism. JAMA. 2015;314(18):1913-4. Farge D, Frere C, Connors JM, et al. 2019 International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. The Lancet Oncology. 2019;20(10):e566-581. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020 Feb 10;38(5):496-520. Khorana AA, Yannicelli D, McCrae KR, et al. Evaluation of US prescription patterns: are treatment guidelines for cancer-associated venous thromboembolism being followed? Thromb Res. 2016 Sep;145:51-3. Disclosures No relevant conflicts of interest to declare.

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