Anticoagulation Therapy in Cancer Patients with Thrombosis in the Outpatient Sector of Germany (The CERTIFICAT Initiative)—German Practice of Anticoagulation Therapy of Cancer Patients with Thrombosis

Abstract Objective This article aims to investigate the reality of anticoagulation treatment for cancer patients with thrombosis in the outpatient sector of Germany. Methods For the analysis period 2012 to 2015, anonymized data from 4.1 million statutory insured patients were analyzed. Cancer patients with incident thrombosis and an outpatient prescription of anticoagulant drugs were identified and evaluated for three subsequent quarters with regard to anticoagulant use. Results A total of 7,313 cancer patients with incident thrombosis (ICD-10: I80*) were evaluated. About, 90% of patients with thromboses were diagnosed and treated in the ambulatory sector. More than 80% of the prescriptions were issued by general practitioners. And 57% of patients were anticoagulated predominantly (>50% of the time) with different low-molecular-weight heparins (LMWHs), 24% predominantly with vitamin K antagonists (VKAs), and 17% with direct oral anticoagulants (DOACs). Anticoagulants were prescribed for an average of 4.5 months. LMWH had a substantially longer prescription period (90–135 days) than VKA (53 days) or DOAC (47 days). Gastrointestinal bleeding in conjunction with hospitalization was documented in 1.76% of patients with a range of 1.3 to 3% for the different LMWHs. Conclusion The prescription practice documented by this representative and comprehensive evaluation demonstrates an anticoagulation duration in accordance with the guidelines, although the choice of the respective anticoagulant was often not in compliance with the contemporary label or guidelines.

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Direct Oral Anticoagulants in Cancer Patients. Time for a Change in Paradigm

Cancers ◽

10.3390/cancers12051144 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1144 ◽

Cited By ~ 1

Author(s):

Marek Z. Wojtukiewicz ◽

Piotr Skalij ◽

Piotr Tokajuk ◽

Barbara Politynska ◽

Anna M. Wojtukiewicz ◽

...

Keyword(s):

Cancer Patients ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Current Evidence ◽

Low Molecular Weight ◽

Treatment And Prevention ◽

Prevention Of Cancer ◽

Selection Of

Thrombosis is a more common occurrence in cancer patients compared to the general population and is one of the main causes of death in these patients. Low molecular weight heparin (LMWH) has been the recognized standard treatment for more than a decade, both in cancer-related thrombosis and in its prevention. Direct oral anticoagulants (DOACs) are a new option for anticoagulation therapy. Recently published results of large randomized clinical trials have confirmed that DOAC may be a reasonable alternative to LMWH in cancer patients. The following review summarizes the current evidence on the safety and efficacy of DOAC in the treatment and prevention of cancer-related thrombosis. It also draws attention to the limitations of this group of drugs, knowledge of which will facilitate the selection of optimal therapy.

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Low-Molecular-Weight Heparin in Cancer Patients: Overview and Indications

Hämostaseologie ◽

10.1055/s-0039-1677796 ◽

2019 ◽

Vol 39 (01) ◽

pp. 067-075 ◽

Cited By ~ 3

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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Safety and Feasibility of Treatment with Rivaroxaban in Children for Non-Routine Indications: A Case Series Analysis

Blood ◽

10.1182/blood.v128.22.5014.5014 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5014-5014 ◽

Cited By ~ 1

Author(s):

Kathryn E. Dickerson ◽

Ravi Sarode ◽

Ayesha Zia

Keyword(s):

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Case Series ◽

Bleeding Complications ◽

Fixed Dose ◽

The Mean ◽

Recurrent Vte

Background. Anticoagulation therapy is the cornerstone of acute treatment of venous thromboembolism (VTE) and for prevention of recurrent VTE. The need for anticoagulation is increasing in children, largely in part due to increasing VTE rates. Conventional anticoagulants, including heparin, low-molecular weight heparins (LMWH), Fondaparinux, and vitamin K antagonists (VKA) are widely used in children but have limitations. Standard of care management with these agents is plagued with the trade-off between daily or twice daily injections or frequent monitoring of therapeutic effect. The advent of direct oral anticoagulants (DOACs) have catalyzed significant changes in the therapeutic landscape of VTE management. DOACs have been evaluated for safety and efficacy in large, randomized controlled trials in the treatment and prevention of VTE in adults, with results that are comparable to conventional therapy. None of the current DOACs have FDA-approved indications and dosing in children yet. Off-label use of these agents is largely based on adult data and doses, and is increasing at many Children's Hospitals across US. Rivaroxaban, a DOAC, is a factor Xa inhibitor with predictable pharmacokinetic and pharmacodynamics properties. Methods. We describe a case series of 8 unique pediatric cases, treated with Rivaroxaban, for a variety of non-routine indications, due either to adverse effects, intolerability of LMWH or VKA or the need for ongoing, long term anticoagulation. Rivaroxaban was started after informed consent and assent from parents or patients respectively, and was initiated at a fixed dose but titrated to a final dose after monitoring of trough and peak Rivaroxaban levels (Aniara, West Chester,OH, USA). Results. The mean age of patients in this case series is 14 years (median: 16, range 3-17) (see Table). The most common indication to use Rivaroxaban was the need for long term anticoagulation after having completed therapeutic anticoagulation, except in two patients, one of whom developed warfarin skin necrosis due to protein C deficiency and another with heparin induced thrombocytopenia. Only two patients needed dose adjustments to achieve target trough and peak drug levels. The mean duration of follow-up is 9 months (median= 5.5; range 3-24) (see Table) at this time. None of the patients developed recurrent VTE while on Rivaroxaban. A soft tissue traumatic bleed occurred in one patient which was treated with holding off the drug for 48 hours. No other bleeding complications were observed. Conclusions. Clinical application of DOACs in a real world clinical setting, including strong thrombophilia and malignancy, results in treatment profile of high efficacy and safety in children; however, larger studies are needed to validate these findings. Disclosures Sarode: CSL Behring: Consultancy, Honoraria.

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Cancer-associated venous thromboembolism: Burden, mechanisms, and management

Thrombosis and Haemostasis ◽

10.1160/th16-08-0615 ◽

2017 ◽

Vol 117 (02) ◽

pp. 219-230 ◽

Cited By ~ 110

Author(s):

Cihan Ay ◽

Ingrid Pabinger ◽

Alexander T. Cohen

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Performance Status ◽

Direct Oral Anticoagulants ◽

Treatment Options ◽

Cancer Site ◽

Related Factors ◽

Venous Diseases

SummaryVenous thromboembolism (VTE) is a significant health problem in the general population but especially in cancer patients. In this review, we discuss the epidemiology and burden of the disease, the pathophysiology of cancer-associated VTE, and the clinical treatment options for both primary prevention and acute treatment. Overall, the development of VTE in cancer patients is related to increases in morbidity, mortality, and medical costs. However, the incidence of cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia, comorbidities, performance status, history of venous diseases), tumour-related factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g. surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes) and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for the risk of VTE in cancer patients and have been used to enhance risk stratification. Evidence suggests that cancer itself is associated with a state of hypercoagulability, driven in part by the release of procoagulant factors, such as tissue factor, from malignant tissue as well as by inflammation-driven activation of endothelial cells, platelets, and leukocytes. In general, low-molecular-weight heparin (LWMH) monotherapy is the standard of care for the management of cancer-associated VTE, as vitamin K antagonists are less effective in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially promising treatment option for cancer patients with VTE, but recommendations concerning the routine use of DOACs should await head-to-head studies with LMWH.

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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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Practical Considerations for the Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029616634886 ◽

2016 ◽

Vol 23 (1) ◽

pp. 5-19 ◽

Cited By ~ 7

Author(s):

Zachary Stacy ◽

Sara Richter

Keyword(s):

Atrial Fibrillation ◽

Treatment Guidelines ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Significant Risk ◽

The United States ◽

Assessment Tools ◽

Long Term Outcome

Atrial fibrillation (AF) is a significant risk factor for stroke and peripheral thromboembolic events (TEs). Preventing blood clots in the heart to reduce stroke and TE risk is a key goal of AF therapy. Traditional stroke risk assessment tools for patients with nonvalvular AF include the CHADS2 and CHA(2)DS(2)-VASc scores, while long-term outcome data with the newer direct oral anticoagulants (DOACs) are emerging. The goals of this review were to assess traditional therapies and existing treatment guidelines and to discuss key pharmacologic properties of the DOACS, noting how these may benefit at-risk patients with AF. This narrative review was developed on the basis of the authors’ clinical knowledge, extensive reading of the literature, and broad pharmacy experience in the management of patients with AF. Limitations of oral vitamin K antagonists (VKAs) include slow onset of action, the need for regular monitoring of their anticoagulation effect, significant food and drug interactions, and unpredictable dose–response properties. Key clinical trial data led to the approvals of apixaban, dabigatran etexilate, edoxaban, and rivaroxaban in the United States to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF. With predictable pharmacologic properties and limited drug and/or dietary interactions, the DOACs offer several benefits over traditional oral anticoagulation therapy with VKA. However, they have limitations, including the absence of immediate reversal agents and limited options for monitoring their anticoagulation effects in clinical practice. As experience with the use of DOACs grows, optimized treatment regimens and improved patient care are expected.

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

Phlebologie ◽

10.1055/s-0038-1625439 ◽

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.

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

Hematology ◽

10.1182/asheducation-2017.1.136 ◽

2017 ◽

Vol 2017 (1) ◽

pp. 136-143 ◽

Cited By ~ 2

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.

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Anticoagulation in Deep Venous Thrombosis: Current Trends in the Era of Non- Vitamin K Antagonists Oral Anticoagulants

Current Pharmaceutical Design ◽

10.2174/1381612826666200420150517 ◽

2020 ◽

Vol 26 (23) ◽

pp. 2692-2702 ◽

Cited By ~ 1

Author(s):

Panteleimon E. Papakonstantinou ◽

Costas Tsioufis ◽

Dimitris Konstantinidis ◽

Panagiotis Iliakis ◽

Ioannis Leontsinis ◽

...

Keyword(s):

Cancer Patients ◽

Vitamin K ◽

Safety Profile ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Bleeding Risk ◽

Efficacy And Safety ◽

Anticoagulation Management ◽

Oral Agents

: Anticoagulation therapy is the cornerstone of treatment in acute vein thrombosis (DVT) and it aims to reduce symptoms, thrombus extension, DVT recurrences, and mortality. The treatment for DVT depends on its anatomical extent, among other factors. Anticoagulation therapy for proximal DVT is clearly recommended (at least for 3 months), while AT for isolated distal DVT should be considered, especially in the presence of high thromboembolic risk factors. The optimal anticoagulant and duration of therapy are determined by the clinical assessment, taking into account the thromboembolic and bleeding risk in each patient in a case-by-case decision making. Non-Vitamin K antagonists oral anticoagulants (NOACs) were a revolution in the anticoagulation management of DVT. Nowadays, NOACs are considered as first-line therapy in the anticoagulation therapy for DVT and are recommended as the preferred anticoagulant agents by most scientific societies. NOACs offer a simple route of administration (oral agents), a rapid onset-offset of their action along with a good efficacy and safety profile in comparison with Vitamin K Antagonists (VKAs). However, there are issues about their efficacy and safety profile in specific populations with high thromboembolic and bleeding risks, such as renal failure patients, active-cancer patients, and pregnant women, in which VKAs and heparins were the standard care of treatment. Since the available data are promising for the use of NOACs in end-stage chronic kidney disease and cancer patients, several ongoing randomized trials are currently trying to solve that issues and give evidence about the safety and efficacy of NOACs in these populations.

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Direct oral anticoagulants (DOAC) for prevention of recurrent arterial or venous thromboembolic events (ATE/VTE) in myeloproliferative neoplasms

Annals of Hematology ◽

10.1007/s00277-020-04350-6 ◽

2020 ◽

Author(s):

Karlo Huenerbein ◽

Parvis Sadjadian ◽

Tatjana Becker ◽

Vera Kolatzki ◽

Eva Deventer ◽

...

Keyword(s):

Myeloproliferative Neoplasms ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Thromboembolic Events ◽

Number Of Patients ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic

AbstractIn patients with BCR-ABL-negative myeloproliferative neoplasms (MPN), arterial or venous thromboembolic events (ATE/VTE) are a major burden. In order to control these complications, vitamin K antagonists (VKA) are widely used. There is no robust evidence supporting the use of direct oral anticoagulants (DOAC) in MPN patients. We therefore compared the efficacy and safety of both anticoagulants in 71 cases from a cohort of 782 MPN patients. Seventy-one of 782 MPN patients (9.1%) had ATE/VTE with nine ATE (12.7%) and 62 VTE (87.3%). Forty-five of 71 ATE/VTE (63.4%) were treated with VKA and 26 (36.6%) with DOAC. The duration of anticoagulation therapy (p = 0.984), the number of patients receiving additional aspirin (p = 1.0), and the proportion of patients receiving cytoreductive therapy (p = 0.807) did not differ significantly between the VKA and DOAC groups. During anticoagulation therapy, significantly more relapses occurred under VKA (n = 16) compared to DOAC treatment (n = 0, p = 0.0003). However, during the entire observation period of median 3.2 years (0.1–20.4), ATE/VTE relapse-free survival (p = 0.2) did not differ significantly between the two anticoagulants. For all bleeding events (p = 0.516) or major bleeding (p = 1.0), no significant differences were observed between VKA and DOAC. In our experience, the use of DOAC was as effective and safe as VKA, possibly even potentially beneficial with a lower number of recurrences and no increased risk for bleedings. However, further and larger studies are required before DOAC can be routinely used in MPN patients.

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