scholarly journals The Role of Direct Oral Anticoagulants in Treatment of Cancer-Associated Thrombosis

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 271 ◽  
Author(s):  
Hanny Al-Samkari ◽  
Jean Connors
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Patient Population ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Population Data ◽  
Standard Of Care ◽  
Published Data ◽  
Onset Of Action ◽  
Recurrent Vte

Venous thromboembolism (VTE) complicates the clinical course of approximately 5–10% of all cancer patients. Anticoagulation of the cancer patient often presents unique challenges as these patients have both a higher risk of recurrent VTE and a higher risk of bleeding than patients without cancer. Although low molecular weight heparins (LMWH) are the standard of care for the management of cancer-associated VTE, their use requires once or twice daily subcutaneous injections, which can be a significant burden for many cancer patients who often require a long duration of anticoagulation. The direct oral anticoagulants (DOACs) are attractive options for patients with malignancy. DOACs offer immediate onset of action and short half-lives, properties similar to LMWH, but the oral route of administration is a significant advantage. Given the higher risks of recurrent VTE and bleeding, there has been concern about the efficacy and safety of DOACs in this patient population. Data are now emerging for the use of DOACs in the cancer patient population from dedicated clinical trials. While recently published data suggest that DOACs hold promise for the treatment of cancer associated VTE, additional studies are needed to establish DOACs as the standard-of-care treatment. Many such studies are currently underway. The available data for the use of DOACs in the treatment of cancer-associated VTE will be reviewed, focusing on efficacy, safety, and other considerations relevant to the cancer patient.

scholarly journals Recent Advances in the Management of Cancer-Associated Thrombosis: New Hopes but New Challenges

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 71 ◽  
Author(s):  
Corinne Frere ◽  
Ilham Benzidia ◽  
Zora Marjanovic ◽  
Dominique Farge
Keyword(s):  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Standard Of Care ◽  
Primary Prophylaxis ◽  
Rapid Onset ◽  
Term Therapy ◽  
Onset Of Action ◽  
Recent Advances ◽  
Cancer Associated Thrombosis

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients and leads to a significant increase in health care costs. Cancer patients often suffer from multiple co-morbidities and have both a greater risk of VTE recurrence and bleeding compared to non-cancer patients. Anticoagulation is therefore challenging. For many years, long-term therapy with Low-Molecular-Weight Heparin (LMWH) was the standard of care for the management of cancer-associated VTE. Direct oral anticoagulants (DOAC), which offer the convenience of an oral administration and have a rapid onset of action, have recently been proposed as a new option in this setting. Head-to-head comparisons between DOAC and LMWHs for the treatment of established VTE are now available, and data on the efficacy and safety of these drugs for primary prophylaxis of VTE in ambulatory cancer patients receiving systemic anticancer therapy are emerging. This narrative review aims to summarize the main recent advances in the prevention and treatment of cancer-associated VTE, including recent data on the use of individualized factors to stratify the risk of VTE in each individual patient, quality-of-life in patients treated with LMWH, and the place that DOACs will likely take in the cancer-associated VTE management landscape.

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

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

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

scholarly journals Direct Oral Anticoagulant Drugs: On the Treatment of Cancer-Related Venous Thromboembolism and their Potential Anti-Neoplastic Effect

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 46 ◽  
Author(s):  
Francesco Grandoni ◽  
Lorenzo Alberio
Keyword(s):  
Cancer Patients ◽  
Therapeutic Option ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Published Data ◽  
Factor X ◽  
Factor Ii ◽  
Anticoagulant Drugs ◽  
Treatment Paradigm ◽  
Diagnosis Of Cancer

Cancer patients develop a hypercoagulable state with a four- to seven-fold higher thromboembolic risk compared to non-cancer patients. Thromboembolic events can precede the diagnosis of cancer, but they more often occur at diagnosis or during treatment. After malignancy itself, they represent the second cause of death. Low molecular weight heparins are the backbone of the treatment of cancer-associated thromboembolism. This treatment paradigm is possibly changing, as direct oral anticoagulants (DOACs) may prove to be an alternative therapeutic option. The currently available DOACs were approved during the first and second decades of the 21st century for various clinical indications. Three molecules (apixaban, edoxaban and rivaroxaban) are targeting the activated factor X and one (dabigatran) is directed against the activated factor II, thrombin. The major trials analyzed the effect of these agents in the general population, with only a small proportion of cancer patients. Two published and several ongoing studies are specifically investigating the use of DOACs in cancer-associated thromboembolism. This article will review the current available literature on the use of DOACs in cancer patients. Furthermore, we will discuss published data suggesting potential anti-cancer actions exerted by non-anticoagulant effects of DOACs. As soon as more prospective data becomes available, DOACs are likely to be considered as a potential new therapeutic option in the armamentarium for patients suffering of cancer-associated thromboembolism.

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

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

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

scholarly journals Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial.

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Cecilia Becattini ◽  
Rupert Bauersachs ◽  
Giorgio Maraziti ◽  
Laurent Bertoletti ◽  
Alexander Cohen ◽  
...  
Keyword(s):  
Renal Function ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Metastatic Cancer ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Patients With Cancer ◽  
Relative Safety ◽  
Recurrent Vte

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We run a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 ml/minute; 275 patients) and mild (between 60-89 ml/minute; 444 patients). In 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06, 95% CI 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR 0 .67, 95% CI 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR 0.27, 95% CI 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR 2.84, 95% CI 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin.

Direct oral anticoagulants in patients with cancer

2019 ◽  
Vol 76 (14) ◽  
pp. 1019-1027
Author(s):  
John B Bossaer ◽  
Kelly L Covert
Keyword(s):  
Atrial Fibrillation ◽  
Cancer Patients ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Safety Data ◽  
Standard Of Care ◽  
Patients With Cancer ◽  
Thrombotic Complications

AbstractPurposeThis review summarizes the available evidence concerning direct oral anticoagulant (DOAC) use to treat venous thromboembolism (VTE) in patients with cancer as well as pertinent safety data on the use of DOACs in patients with both cancer and atrial fibrillation.SummaryThe introduction of DOACs into clinical practice changed the way thrombotic complications are managed and prevented in diverse patient populations, including VTE and atrial fibrillation. Low-molecular-weight heparins have been the standard of care for treating VTE in cancer patients due to superiority over vitamin K antagonists in preventing recurrent VTE. Therefore, widespread DOAC use for VTE in patients with active cancer has not been adopted.ConclusionRecent randomized clinical trials (SELECT-D, Hokusai VTE Cancer) have provided evidence that DOACs may have a role in treating VTE in cancer patients.

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

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

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

P5239Cost-effectiveness of direct oral anticoagulants for cancer-associated venous thromboembolism

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J King ◽  
S Bhat ◽  
L J Heath ◽  
C G Derington ◽  
Z Yu ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cost Effectiveness ◽  
Relative Risk ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cost Effective ◽  
Low Molecular Weight ◽  
Cost Effectiveness Ratio ◽  
Major Bleed ◽  
Recurrent Vte

Abstract Background Direct oral anticoagulants (DOACs) are at least as effective as low-molecular weight heparins (LMWH) at preventing recurrence after cancer-associated venous thromboembolism (CA-VTE). DOACs are also oral and far less costly, but they may confer a higher bleeding risk than LMWH. Purpose To estimate the cost-effectiveness of DOACs and LMWHs for CA-VTE. Methods We developed a health state transition model to estimate recurrent VTE, bleeding events, quality-adjusted life years (QALY), and direct healthcare costs (2018 United States dollars) associated with DOACs vs. LMWH use. The model had four states: (1) long-term anticoagulation (first 3 months after VTE), (2) extended anticoagulation (more than 3 months after VTE), (3) off anticoagulants, and (4) death. We used a United States healthcare sector perspective, 3-month cycle length, and 1-year time horizon. Event probabilities were derived from the Hokusai Cancer VTE trial and other literature. Event and medication costs were obtained from national sources. We used a threshold of less than $50,000 per QALY gained to define cost-effectiveness. Results Compared to LMWH, DOACs were less costly (mean costs: $8,477 vs. $33,917 per year) and similarly effective (mean QALY: 0.616 vs. 0.622). The incremental cost-effectiveness ratio was $4,479,374 per QALY gained with LMWH, indicating that DOACs are cost-effective (Table 1). In threshold analyses, LMWH therapy only became cost-effective when DOAC recurrent VTE risk increased to at least 72% (relative risk vs. LMWH, 6.19) or DOAC clinically relevant bleeding increased to at least 39% (relative risk vs. LMWH, 10.09). Scenarios Recurrent VTE, % Major bleed, % Mean difference DOAC − LMW ICER DOAC LMWH Relative Risk DOAC LMWH Relative Risk Cost QALY Base case 8.1 11.6 0.71 6.8 4.0 1.75 −$25,440 (−26,496, −24,274) −0.006 (−0.019, 0.008) $4,479,374 DOAC outcome rate threshold at which LMWH becomes cost-effective*   Recurrent VTE 71.5 11.7 6.19 – – – −$6,064 (−7,534, −4,627) −0.121 (−0.136, −0.108) $49,886   Major Bleed – – – 38.9 4.0 10.09 −$2,192 (−3,400, −704) −0.044 (−0.056, −0.030) $49,878 DOAC = direct oral anticoagulant, ICER = incremental cost-effectiveness ratio, LMWH = low-molecular-weight heparin, VTE = venous thromboembolism. Values are mean (95% Uncertainty Interval). Uncertainty was derived from 1,000 stochastic model iterations. *Represents the minimum increased risk with DOAC that would result in LMWH achieving an ICER <$50K per QALY gained. Conclusion In this simulation study, DOACs were a cost-effective oral alternative to LMWH for the treatment of CA-VTE. For LMWH to be cost-effective, DOAC event rates needed to be far higher than what is likely to be observed in clinical practice. Acknowledgement/Funding Agency for Health Research and Quality R18HS026156

Examination of the Effectiveness of Direct Oral Anticoagulants in Comparison to Warfarin in an Obese Population

2021 ◽  
pp. 875512252110641
Author(s):  
Rachel M. Watson ◽  
Carmen B. Smith ◽  
Erica F. Crannage ◽  
Laura M. Challen
Keyword(s):  
Primary Outcome ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Class Iii ◽  
Vein Thrombosis ◽  
Class Iii Obesity ◽  
Recurrent Vte ◽  
The Individual ◽  
Deep Vein

Background: While commonly prescribed today, direct oral anticoagulants (DOACs) have historically been avoided in patients with class III obesity or a weight >120 kg due to limited literature regarding the efficacy and safety in this population. Objective: The overall objective was to examine the effectiveness of DOACs compared to warfarin in a population with obesity. Methods: Patients with a diagnosis of venous thromboembolism (VTE) or atrial fibrillation and a body mass index (BMI) ≥35 kg/m2 from August 1, 2015, to August 1, 2020, were included in this retrospective cohort study. Patients receiving a DOAC were matched in a 1:2 ratio to warfarin. The primary outcome was a composite of stroke or recurrent VTE. Secondary outcomes included the individual components of the primary outcome, hospitalization for bleed, and the primary outcome in patients with a BMI ≥40 kg/m2. Results: A total of 162 patients were included, with 54 and 108 in the DOAC and warfarin groups, respectively. Baseline BMI was similar between groups (45.7 kg/m2 for DOACs vs 43.8 kg/m2 for warfarin), with approximately 70% of patients having a BMI ≥40 kg/m2. The primary outcome occurred in 1 patient (1.9%) in the DOAC group and 2 patients (1.9%) in the warfarin group. The DOAC group had a higher, nonsignificant incidence of bleeding (5.6% vs 0.9%, P = 0.11). There was no difference between groups in incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke in patients with a BMI ≥40 kg/m2. Conclusion: DOACs may be as efficacious as warfarin in the prevention of stroke or recurrent VTE in patients with a BMI of ≥35 kg/m2. Prospective, randomized trials are warranted to further assess the efficacy and safety of DOACs in this population.

ANTICOAGULANT THERAPY IN CANCER PATIENTS WITH ATRIAL FIBRILLATION. CONSIDERING AGE FACTOR

2020 ◽  
pp. 99-106
Author(s):  
В. И. Потиевская ◽  
А. А. Ахобеков ◽  
М. Ф. Баллюзек
Keyword(s):  
Atrial Fibrillation ◽  
Cancer Patients ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Current Data ◽  
Related Factors ◽  
Age Related ◽  
Liver And Kidney ◽  
After Cancer

Рассматривается современное состояние вопроса выбора антикоагулянтной терапии при фибрилляции предсердий (ФП) у онкологических больных. Отмечается, что сложность выбора антикоагулянта при злокачественных новообразованиях (ЗНО) определяется такими факторами, как коморбидные сердечно-сосудистые заболевания, нарушения функции печени и почек, метаболические дисфункции, свойственные, прежде всего, пациентам старшей возрастной группы. Приводятся актуальные данные по оценке риска геморрагических и тромбоэмболических осложнений ФП при ЗНО в аспекте возраста. Обсуждаются возможные причины увеличения риска развития ФП во время и после лечения ЗНО, в том числе и в связи с возраст-ассоциированностью этих патологий. Рассмотрены вопросы выбора антикоагулянтов у пациентов, находящихся на активной противоопухолевой терапии, особенно на препаратах из группы прямых оральных антикоагулянтов (ПОАК). Согласно данным обсервационных исследований, именно ПОАК являются перспективным, относительно безопасным и эффективным выбором для онкологических пациентов с ФП, в связи с чем их применение должно активно изучаться в рандомизированных клинических исследованиях с учетом фактора возраста. Подчеркивается, что подбор схемы антикоагулянтной терапии у пациентов с ФП и ЗНО требует междисциплинарного участия кардиологов и онкологов, а часто и гериатров, чтобы индивидуализировать лечение и предложить наиболее эффективную терапию. The current issue of the choice of anticoagulant therapy of atrial fibrillation (AF) in cancer patients is considered. It is noted that the difficulty of choosing an anticoagulant in malignancies is largely determined by age-related factors, such as comorbid cardiovascular diseases, liver and kidney dysfunction, metabolic disorders common for in elderly patients. Current data on the risk assessment of hemorrhagic and thromboembolic complications of AF in cancer patients in the aspect of age presented. During and after cancer treatment, the risk of developing AF can increase, also in connection with the age-associated pathology. Possible reasons of it are discussed. The choice of different anticoagulants groups in patients treated with anticancer therapy, including direct oral anticoagulants (DOAC) is considered. According to available data from observational studies, it is the DOAC that is a promising, relatively safe and effective choice for cancer patients with AF, and therefore their use should be actively studied in randomized trials, considering the factor of age. It is particularly noted that solving this problem requires the interdisciplinary involvement of cardiologists, oncologists, and sometimes, geriatrics, to individualize treatment for each case and to offer the most effective therapy.

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