First-Line Therapies for VTE Treatment and Secondary Prophylaxis in Patients With Cancer: A New Direction

2018 ◽  
Vol 33 (3) ◽  
pp. 356-363
Author(s):  
Samantha M. Vogel ◽  
Leticia V. Smith ◽  
Evan J. Peterson
Keyword(s):  
Venous Thromboembolism ◽  
English Language ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Secondary Prophylaxis ◽  
Careful Consideration ◽  
Patients With Cancer ◽  
Study Selection ◽  
Meta Analyses

Objective: To review evidence behind anticoagulants in cancer-associated venous thromboembolism (VTE) with a focus on low-molecular-weight heparins (LMWH) and the role of direct oral anticoagulants (DOACs). Data Sources: PubMed was searched using terms “venous thromboembolism,” “cancer,” and “anticoagulation.” This search was restricted to clinical trials, meta-analyses, and subgroup analyses. Additional references were identified from reviewing literature citations. Study Selection: English-language prospective and retrospective studies assessing the efficacy and safety of LMWH and DOACs in patients with cancer. Data Analysis: Several trials were analyzed that compared anticoagulation therapies for prevention of recurrent VTE in patients with cancer. Many studies comparing LMWH and vitamin K antagonists (VKAs) found nonsignificant differences between therapies. A single study demonstrated that LMWHs are superior to VKAs. This evidence supporting LMWH for long-term VTE treatment in patients with cancer is based on comparison to VKA, but results are limited by methodological issues, and the benefit of LMWH may be driven by poor control. Subanalyses of DOAC trials suggest these are equally or more effective as VKA in cancer, but this conclusion is underpowered. Conclusion: DOACs have the potential to bypass many challenges with traditional therapy. After analyzing the evidence available, we conclude that after careful consideration of risks and benefits, use of DOACs for VTE treatment are a reasonable option in patients with cancer.

scholarly journals Direct oral anticoagulants: now also for prevention and treatment of cancer-associated venous thromboembolism?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 136-143 ◽  
Author(s):  
Ingrid Pabinger ◽  
Julia Riedl
Keyword(s):  
Venous Thromboembolism ◽  
Primary Prevention ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Similar Efficacy ◽  
Prevention And Treatment ◽  
History Of ◽  
Meta Analyses

Abstract Data on specific studies in cancer patients using direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE) are still scarce. For preventing VTE with DOACs, current experience is still very limited, so definite conclusions cannot yet be drawn. However, DOACs have so far been compared with vitamin K antagonists (VKAs) in patients with acute VTE in 5 studies, and several hundreds of patients included in these studies had either active cancer, a history of cancer, or a new occurrence of cancer during the course of disease. Meta-analyses have revealed an at least similar efficacy and safety profile of DOACs compared with VKAs. A number of studies of cancer patients investigating primary prevention and treatment are underway, and some will be finalized soon. Nevertheless, we might need further trials, specifically on the prevention of VTE in patients who are at particularly high risk. This article also includes a personal opinion on the use of DOACs in cancer patients. In conclusion, the currently available data show that DOACs might be safe and efficacious in the treatment of VTE, however, this has yet to be proven in specifically designed trials in patients with cancer. With regard to prevention, thus far, even less data exist, and the outcomes of the ongoing studies have to be evaluated before DOACs may be used for primary prevention.

scholarly journals Treatment of Venous Thromboembolism in Special Populations with Direct Oral Anticoagulants

2020 ◽  
Vol 120 (06) ◽  
pp. 899-911
Author(s):  
Roisin Bavalia ◽  
Saskia Middeldorp ◽  
Gerhard Weisser ◽  
Christine Espinola-Klein
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Phase Iii Trials ◽  
Guidance Documents ◽  
Phase Iii Studies ◽  
Dose Reductions

AbstractAs a result of the successful completion of their respective phase III studies compared with vitamin K antagonists (VKAs), four direct oral anticoagulants (DOACs) have been approved for the treatment and secondary prevention of venous thromboembolism (VTE). These DOACs—apixaban, dabigatran, edoxaban, and rivaroxaban—have subsequently seen a steady uptake among clinicians since their approval. Despite the suitability of DOACs for a broad range of patients, they are not appropriate in certain situations, whereas in others they require additional considerations such as dose reductions. Subanalyses of phase III trials and studies on specific VTE patient populations have been conducted to evaluate the safety and efficacy of the DOACs in a broad range of settings, such as patients with renal impairment, patients with cancer, patients of childbearing potential, patients with multiple comorbidities and pediatric patients. Furthermore, many recent guidance documents from important hematological societies and other specialists have incorporated several of these developments. These documents also identify the patients for whom DOACs are not suitable and where traditional anticoagulation options such as heparins or VKAs should be considered instead. This review provides an overview of key VTE patient subgroups, the clinical evidence supporting the use of anticoagulation in these patients, and a discussion of the most appropriate approaches to their management, including considerations such as dosing, acute and extended treatment durations, and DOAC selection.

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.

scholarly journals Arguments for Using Direct Oral Anticoagulants in Cancer-Related Venous Thromboembolism

Healthcare ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1287
Author(s):  
Roxana Mihaela Chiorescu ◽  
Mihaela Mocan ◽  
Mirela Anca Stoia ◽  
Anamaria Barta ◽  
Cerasela Mihaela Goidescu ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Randomized Controlled Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Controlled Trials ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
First Choice ◽  
Meta Analyses

(1) Background: Patients with cancer with a hypercoagulable state present an increased incidence of venous thromboembolism (VTE). Neoplastic patients with concurrent VTE undergoing anticoagulant treatment face a series of issues. (2) The aim of the present paper is to systematically summarize current VTE management in patients with neoplasia and to review the current clinical evidence from meta-analyses of randomized controlled trials and guidelines regarding the administration of direct oral anticoagulants (DOACs) for cancer-associated VTE. (3) Search Strategy: We performed a review on meta-analyses of randomized controlled trials and guidelines in favor of the administration of DOACs in patients with cancer-associated VTE published in the last 6 years in the Medline (PubMed) and Embase databases. (4) Results: 21 meta-analyses, 14 randomized controlled studies comparing DOACs to VKAs and LMWH, and 7 national and international guidelines were identified. We identified five studies that show the antineoplastic effect of DOAC on experimental models. (5) Conclusions: DOACs can be seen as the first choice for VTE treatment in neoplastic patients who have a low risk of bleeding, who do not have severe renal impairment, and who are not undergoing treatments that could interact with DOAC’s mechanism of action.

P690Incidence of events between vitamin K antagonists and direct oral anticoagulants in patients with cancer

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Pardo Sanz ◽  
L M Rincon ◽  
G De Lara ◽  
A Tamayo ◽  
L C Belarte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Patients With Cancer

Abstract Background Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We aimed to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with breast cancer. We also compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. Methods It is an ambispective observational multicentric study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain in the period 2011–2018. A total of 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. The incidence of thromboembolic and major bleeding events according to the antithrombotic strategy with VKAs or DOACs was evaluated in the cohort of 637 patients with cancer. Analysis were conducted using SPSS software V.22.0 and R V.3.5.1, with a two-tailed significance value of 0.05. Results Mean follow-up was 3.1 years. Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. There was no evidence that the incidence of ischemic stroke/systemic embolism differed between patients with cancer treated with AVK and DOAC after CHA2DS2-VASc adjustment: HR 0.91 (95% CI, 0.42–1.99). In addition, no significant differences in the incidence of major bleeding events were found between DOACs and VKA after adjustment for HAS-BLED score: HR 1.53 (95% CI, 0.93–2.53) (Figure 3). Gastrointestinal bleeding was the main source of haemorrhages in both groups (45% of bleedings among patients treated with DOACs and, 37% in VKAs group). Metastatic disease or active chemotherapy were studied as potential covariates but none of them posed any relevant change in the result. Kaplan-Meier analysis Conclusions Cancer patients treated with DOACs did not differ versus those treated with VKAs with regards to stroke or systemic embolism in a model adjusted for CHA2DS2-VASc. Neither significant differences were found for bleeding events in a model adjusted for baseline HASBLED.

The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead

2020 ◽  
Vol 25 (5) ◽  
pp. 391-398
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Angelo Leone ◽  
Stefano Poli ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Antiplatelet Therapy ◽  
Oral Anticoagulant ◽  
Acute Coronary Syndromes ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Clinical Scenarios ◽  
Coronary Syndromes

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.

scholarly journals Does aspirin prevent venous thromboembolism?

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 634-641
Author(s):  
Robert Diep ◽  
David Garcia
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Secondary Prophylaxis ◽  
Treatment Modalities ◽  
Surgical Patient ◽  
Vein Thrombosis ◽  
Disease Therapy ◽  
Deep Vein ◽  
Arterial Vascular Disease

Abstract Venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) is a well-established cause of morbidity and mortality in the medical and surgical patient populations. Clinical research in the prevention and treatment of VTE has been a dynamic field of study, with investigations into various treatment modalities ranging from mechanical prophylaxis to the direct oral anticoagulants. Aspirin has long been an inexpensive cornerstone of arterial vascular disease therapy, but its role in the primary or secondary prophylaxis of VTE has been debated. Risk-benefit tradeoffs between aspirin and anticoagulants have changed, in part due to advances in surgical technique and postoperative care, and in part due to the development of safe, easy-to-use oral anticoagulants. We review the proposed mechanisms in which aspirin may act on venous thrombosis, the evidence for aspirin use in the primary and secondary prophylaxis of VTE, and the risk of bleeding with aspirin as compared with anticoagulation.

scholarly journals How I treat venous thromboembolism in pregnancy

Blood ◽  
2020 ◽  
Vol 136 (19) ◽  
pp. 2133-2142
Author(s):  
Saskia Middeldorp ◽  
Wessel Ganzevoort
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Total Duration ◽  
Evidence Base ◽  
Pulmonary Angiography ◽  
Patient Specific ◽  
Postthrombotic Syndrome ◽  
Computed Tomographic

Abstract One to 2 pregnant women in 1000 will experience venous thromboembolism (VTE) during pregnancy or postpartum. Pulmonary embolism (PE) is a leading cause of maternal mortality, and deep vein thrombosis leads to maternal morbidity, with postthrombotic syndrome potentially diminishing quality of life for a woman’s lifetime. However, the evidence base for pregnancy-related VTE management remains weak. Evidence-based guideline recommendations are often extrapolated from nonpregnant women and thus weak or conditional, resulting in wide variation of practice. In women with suspected PE, the pregnancy-adapted YEARS algorithm is safe and efficient, rendering computed tomographic pulmonary angiography to rule out PE unnecessary in 39%. Low molecular weight heparin (LMWH) in therapeutic doses is the treatment of choice during pregnancy, and anticoagulation (LMWH or vitamin K antagonists [VKAs]) should be continued until 6 weeks after delivery, with a 3-month minimum total duration. LMWH or VKA use does not preclude breastfeeding. Postpartum, direct oral anticoagulants are an option if a woman does not breastfeed and long-term use is intended. Management of delivery, including type of analgesia, requires a multidisciplinary approach and depends on local preferences and patient-specific conditions. Several options are possible, including waiting for spontaneous delivery with temporary LMWH interruption. Prophylaxis for recurrent VTE prevention in subsequent pregnancies is indicated in most women with a history of VTE.

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.

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