Preventing Venous Thromboembolism in Ambulatory Patients with Cancer: A Narrative Review

Venous thromboembolism (VTE) is frequent among patients with cancer. Ambulatory cancer patients starting chemotherapy have a 5% to 10% risk of cancer associated thrombosis (CAT) within the first year after cancer diagnosis. This risk may vary according to patient characteristics, cancer location, cancer stage, or the type of chemotherapeutic regimen. Landmark studies evaluating thrombophrophylaxis with low molecular weight heparin (LMWH) for ambulatory cancer patients have shown a relative reduction in the rate of symptomatic VTE of about one half. However, the absolute risk reduction is modest among unselected patients given a rather low risk of events resulting in a number needed to treat (NNT) of 40 to 50. Moreover, this modest benefit is mitigated by a trend towards an increased risk of bleeding, and the economic and patient burden due to daily injections of LMWH. For these reasons, routine thromboprophylaxis is not recommended by expert societies. Advances in VTE risk stratification among cancer patients, and growing evidence regarding efficacy and safety of direct oral anticoagulants (DOACs) for the treatment and prevention of CAT have led to reconsider the paradigms of this risk–benefit assessment. This narrative review aims to summarize the recent evidence provided by randomized trials comparing DOACs to placebo in ambulatory cancer patients and its impact on expert recommendations and clinical practice.

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Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Oncology Reviews ◽

10.4081/oncol.2011.34 ◽

2011 ◽

pp. 191-204

Author(s):

Alpesh N. Amin ◽

Steven B. Deitelzweig

Keyword(s):

At Risk ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Assessment Model ◽

Major Surgery ◽

Medical Illness ◽

Patients With Cancer ◽

Increased Risk ◽

National Quality ◽

American Society

Venous thromboembolism (VTE), a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.

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Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Oncology Reviews ◽

10.4081/oncol.2011.191 ◽

2011 ◽

Vol 5 (3) ◽

pp. 191

Author(s):

Alpesh N. Amin ◽

Steven B. Deitelzweig

Keyword(s):

At Risk ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Assessment Model ◽

Major Surgery ◽

Medical Illness ◽

Patients With Cancer ◽

Increased Risk ◽

National Quality ◽

American Society

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

Current Oncology ◽

10.3747/co.22.2587 ◽

2015 ◽

Vol 22 (2) ◽

pp. 144 ◽

Cited By ~ 33

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.

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Maintenance of Muscle Mass and Cardiorespiratory Fitness to Cancer Patients During COVID-19 Era and After SARS-CoV-2 Vaccine

Frontiers in Physiology ◽

10.3389/fphys.2021.655955 ◽

2021 ◽

Vol 12 ◽

Author(s):

Miguel S. Conceição ◽

Sophie Derchain ◽

Felipe Cassaro Vechin ◽

Guilherme Telles ◽

Guilherme Fiori Maginador ◽

...

Keyword(s):

Cancer Patients ◽

Muscle Mass ◽

Cardiorespiratory Fitness ◽

Exercise Program ◽

Physical Distance ◽

Health Condition ◽

Patients With Cancer ◽

Increased Risk ◽

Wide Range ◽

Risk Of Cancer

There is emerging evidence that decreased muscle mass and cardiorespiratory fitness (CRF) are associated with increased risk of cancer-related mortality. This paper aimed to present recommendations to prescribe effective and safe exercise protocols to minimize losses, maintain or even improve muscle mass, strength, and CRF of the cancer patients who are undergoing or beyond treatment during the COVID-19 era. Overall, we recommend performing exercises with bodyweight, elastic bands, or suspension bands to voluntary interruption (i.e., interrupt the exercise set voluntarily, according to their perception of fatigue, before concentric muscular failure) to maintain or increase muscle strength and mass and CRF during COVID-19 physical distancing. Additionally, rest intervals between sets and exercises (i.e., long or short) should favor maintaining exercise intensities between 50 and 80% of maxHR and/or RPE of 12. In an exercise program with these characteristics, the progression of the stimulus must be carried out by increasing exercise complexity, number of sets, and weekly frequency. With feasible exercises attainable anywhere, modulating only the work-to-rest ratio and using voluntary interruption, it is possible to prescribe exercise for a wide range of patients with cancer as well as training goals. Exercise must be encouraged; however, exercise professionals must be aware of the patient’s health condition even at a physical distance to provide a safe and efficient exercise program. Exercise professionals should adjust the exercise prescription throughout home confinement whenever necessary, keeping in mind that minimal exercise stimuli are beneficial to patients in poor physical condition.

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

F1000Research ◽

10.12688/f1000research.18673.1 ◽

2019 ◽

Vol 8 ◽

pp. 974 ◽

Cited By ~ 3

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.

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

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2020-04-10 ◽

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.

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Low Molecular Weight Heparin Thromboprophylaxis in Ambulatory Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Blood ◽

10.1182/blood.v114.22.490.490 ◽

2009 ◽

Vol 114 (22) ◽

pp. 490-490 ◽

Cited By ~ 11

Author(s):

Nicole M. Kuderer ◽

Thomas L. Ortel ◽

Alok A Khorana ◽

Charles W. Francis ◽

Gary H. Lyman

Keyword(s):

Cancer Patients ◽

Major Bleeding ◽

Research Funding ◽

Absolute Risk ◽

Meta Analysis ◽

Significant Heterogeneity ◽

Bleeding Events ◽

Vte Prophylaxis ◽

Patients With Cancer ◽

Increased Risk

Abstract Abstract 490 Background: Patients with cancer experience an increased risk of venous thromboembolism (VTE) throughout the course of their illness. The risk of VTE appears to be greatest among hospitalized cancer patients, in the perioperative period of major surgery and in those receiving systemic cancer therapies. While encouraged in hospitalized and surgical patients, routine VTE prophylaxis for cancer patients is not recommended in the ambulatory setting except in very selective high risk circumstances. A number of randomized clinical trials (RCTs) of low molecular weight heparin (LMWH) in ambulatory cancer patients have been reported with inconsistent results. Presented here are the results from our updated meta-analysis of LMWH prophylaxis, including recently presented RCTs. Methods: A systematic review of RCTs of VTE prophylaxis with LMWH in ambulatory cancer patients was conducted including the results of published and recently presented trials. Electronic databases including Medline, EMBASE, and Cochrane Library were searched along with meeting abstracts from ASCO and ASH. Eligibility criteria included RCTs of ambulatory cancer patients randomized to LMWH or not and reporting rates of VTE as a primary outcome (primary VTE prophylaxis studies) or a secondary outcome. Dual blinded data extraction was performed with conflict resolution by a third party. Following assessment of heterogeneity, meta-analyses using the method of Mantel and Haenszel were conducted providing weighted summary estimates of both relative risk (RR) and absolute risk (AR) ± 95% confidence intervals (95% CI). Primary study outcomes consist of all reported VTE events and all major bleeds. Most trials did not require VTE screening by imaging, precluding a separate analysis of asymptomatic VTE events. Results: A total of 7 RCTs of LMWH in ambulatory patients with cancer were identified with a total of 2,960 patients including 1,685 receiving LMWH and 1,275 controls. These include 3 RCTs with various solid tumors and one RCT each in breast cancer, lung cancer, pancreatic cancer, and glioblastoma. Patients receiving LMWH experienced 47 VTE events compared to 74 control subjects for crude rates of 2.79% and 5.80%, respectively. No significant heterogeneity was observed across trials (Cochran Q=6.19; I2=3.03; P=.40). The RR for VTE across trials was estimated at 0.54 [95% CI: 0.38 – 0.78; P=.001] while the AR decrease was 2.55% [95% CI: 1.06% – 4.05%; P<.001]. The RR for VTE for the 5 primary VTE prophylaxis trials was 0.50 [95% CI: 0.34 – 0.75; P<.001] with an AR decrease estimated at 2.95% [95% CI: 1.26 – 4.63%; P<.001]. Major bleeding events were reported in 30 patients receiving LMWH compared to 15 control subjects for crude rates of 1.78% and 1.18%, respectively. No significant heterogeneity was observed across trials (Cochran Q=5.50; I2=0.0; P=.481). The RR for major bleeding across trials was estimated at 1.74 [95% CI: 0.95 – 3.18; P=.071], while the AR increase was 0.75% [95% CI: 0.17% – 1.33%; P=.011]. The RR for major bleeding in the 5 primary prophylaxis trials was 2.27 [95% CI: 1.12 – 4.59; P=.022] with AR increase estimated at 1.27% [95% CI: 0.27% – 2.27%; P=.013]. Conclusions: LMWH thromboprophylaxis in ambulatory cancer patients is effective and results in a significant 46% relative risk reduction of venous thromboembolism. However, the risk of VTE is low in this setting and the absolute risk reduction with prophylactic anticoagulation is only 2.6%, while concerns remain about the increase in major bleeding events. Additional research is needed to identify ambulatory cancer patients at increased risk for VTE, in whom VTE prophylaxis may have a more favorable risk-benefit ratio. Disclosures: Ortel: Eisai: Research Funding. Khorana:sanofi-aventis: Consultancy; Eisai: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding. Francis:Eisai: Consultancy, Honoraria.

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

Current Oncology ◽

10.3747/co.22.2586 ◽

2015 ◽

Vol 22 (2) ◽

pp. 133 ◽

Cited By ~ 29

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.

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Venous Thromboembolism and Risk of Cancer in Patients with Dementia: A Danish Population-Based Cohort Study

Journal of Alzheimer s Disease ◽

10.3233/jad-201530 ◽

2021 ◽

pp. 1-13

Author(s):

Cecilia H. Fuglsang ◽

David Nagy ◽

Frederikke S. Troelsen ◽

Dora K. Farkas ◽

Victor W. Henderson ◽

...

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

General Population ◽

Confidence Interval ◽

Absolute Risk ◽

Population Based ◽

First Year ◽

People With Dementia ◽

Increased Risk ◽

Risk Of Cancer

Background: Venous thromboembolism (VTE) may be the first manifestation of occult cancer. Dementia has been linked to reduced cancer risk. Objective: We examined the risk of cancer following VTE in people with dementia in comparison to the risk in the general population. Methods: We conducted a population-based Danish registry-based cohort study following patients with a first-time VTE and a previous or concurrent diagnosis of dementia during the period 1 April 1996 –31 December 2017. We followed the study participants from date of VTE until diagnosis of cancer, death, emigration, or end of study period, whichever came first. The absolute risk of cancer within one year after VTE was computed, treating death as a competing risk. We calculated gender, age, and calendar-period standardized incidence ratios (SIRs) of cancer based on national cancer rates. Results: We followed 3,552 people with dementia and VTE for a median of 1.3 years. Within the first year after VTE, they had a 90%increased risk of cancer in comparison with the general population [SIR: 1.9 (95%confidence interval: 1.6–2.4)]. During subsequent follow-up years, the SIR fell to 0.7 (95%confidence interval: 0.5–0.8). Findings for Alzheimer’s disease and VTE were similar. Conclusion: People with dementia have an increased risk of a cancer diagnosis during the first year following VTE, perhaps related to increased surveillance, and a lower risk thereafter. Overall risk is similar to that of the general population.

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Treatment and secondary prevention of venous thromboembolism in cancer patients

Onkologische Welt ◽

10.1055/s-0038-1630173 ◽

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.

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