Venous Thromboembolism: A Survey of Oral Anticoagulant Preferences in the Treatment of Challenging Patient Populations

Venous thromboembolism (VTE) is a highly morbid condition with several available oral anticoagulant treatment options. Numerous studies have been published comparing warfarin to direct oral anticoagulants; however, several populations remain underrepresented in these reports. We surveyed members of The Venous ThromboEmbolism Network U.S. working group regarding their oral anticoagulant preferences for the treatment of VTE in different and challenging populations. In individuals with VTE and no other medical comorbidities, respondents preferred either rivaroxaban (48.7%) or apixaban (48.7%). Apixaban (53.3%) was preferred in elderly individuals with an increased risk of bleeding. Warfarin was preferred in individuals with liver or kidney dysfunction (42% and 47%), altered metabolism (>55%), and antiphospholipid antibody syndrome (84.2%). Low-molecular-weight heparin was preferred in individuals with malignancy (56.6%), followed by edoxaban (23.7%). These findings may help guide clinicians when choosing an anticoagulant in these challenging situations and demonstrate the urgent need for additional study in these groups.

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Safety and Efficacy of Direct Oral Anticoagulant Therapy in Patients With Cancer

Journal of Pharmacy Practice ◽

10.1177/0897190019896500 ◽

2019 ◽

pp. 089719001989650

Author(s):

Lindsey M. Fovel ◽

Robert W. Seabury ◽

Christopher D. Miller ◽

William Darko ◽

Luke A. Probst ◽

...

Keyword(s):

Venous Thromboembolism ◽

Oral Anticoagulant Therapy ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Minor Bleeding ◽

Safety And Efficacy ◽

Patients With Cancer ◽

Significant Difference

Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with malignancy. The currently available guidelines have shown greater support for utilization of low-molecular-weight heparin (LMWH) over direct oral anticoagulants (DOACs) in cancer-associated VTE. Current data on the safety and efficacy of DOAC therapy in patients with cancer are lacking. Objective: To evaluate the safety and efficacy of the use of DOACs compared to LMWH in patients with cancer. Methods: A retrospective review of outpatient records was completed to identify patients with documented cancer diagnosis and either a DOAC or LMWH as a listed medication. Patients were excluded if they had atrial fibrillation, valvular disease, antiphospholipid antibody syndrome, current pregnancy, body mass index (BMI) >40 kg/m2 or weight >120 kg, severe renal or hepatic impairment, or were on concomitant therapy with a significant interacting medication. The primary outcome was frequency of VTE recurrence, and secondary outcomes included the frequency of major and minor bleeding and other thrombotic events. Results: One hundred fifty-six patients were included in the study population, 78 in both the DOAC and LMWH groups. Venous thromboembolism recurrence occurred in 5 (6.4%) patients in the DOAC group and 8 (10.3%) patients in the LMWH group ( P = .39). There was no significant difference in major or minor bleeding or other thrombotic events between the 2 groups. Conclusion: The frequency of VTE recurrence was similar between DOACs and LMWH in patients with cancer. DOACs may be an alternative agent to LMWH for the prevention of recurrent VTE in patients with cancer.

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The Risk of Recurrent Venous Thromboembolism in Patients with and without Factor V Leiden

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656023 ◽

1997 ◽

Vol 77 (04) ◽

pp. 624-628 ◽

Cited By ~ 139

Author(s):

Sabine Eichinger ◽

Ingrid Pabinger ◽

Andreas Stümpfien ◽

Mirko Hirschl ◽

Christine Bialonczyk ◽

...

Keyword(s):

Oral Anticoagulant Therapy ◽

Oral Anticoagulants ◽

Factor V Leiden ◽

Multicenter Trial ◽

Observation Time ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Factor V ◽

Increased Risk ◽

Recurrent Vte

SummaryThromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anticoagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% Cl 7.8-17) in patients without factor V Leiden and was 10.6% (95% Cl 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral. anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.

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Anticoagulant treatment satisfaction with warfarin and direct oral anticoagulants for venous thromboembolism

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-021-02437-z ◽

2021 ◽

Author(s):

Margaret C. Fang ◽

Alan S. Go ◽

Priya A. Prasad ◽

Jin-Wen Hsu ◽

Dongjie Fan ◽

...

Keyword(s):

Venous Thromboembolism ◽

Treatment Satisfaction ◽

Clinical Characteristics ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Treatment Options ◽

Laboratory Monitoring ◽

Routine Laboratory ◽

Anticoagulant Treatment ◽

The Difference

AbstractTreatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen’s d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p < 0.0001) and ACTS Benefits scores (10.21 v. 9.84, p = 0.046) for DOACs vs. warfarin, respectively. The magnitude of the difference was small (Cohen’s d of 0.29 for ACTS Burdens and 0.12 for ACTS Benefits). Patients taking DOACs for venous thromboembolism were on average more satisfied with anticoagulant treatment than were warfarin users, although the magnitude of the difference was small.

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P4745Concomitant oral anticoagulant and antidepressant therapy in patients with atrial fibrillation and risk of stroke and bleeding: a population based cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.1121 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J J Komen ◽

P Hjemdahl ◽

A K Mantel - Teeuwisse ◽

O H Klungel ◽

B Wettermark ◽

...

Keyword(s):

Atrial Fibrillation ◽

Propensity Score ◽

Oral Anticoagulant ◽

Cox Regression ◽

Oral Anticoagulants ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Increased Risk ◽

Antidepressant Use

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. Antidepressants use is associated with increased risk for stroke and bleeds. Objective To assess the association between antidepressant use in AF patients with oral anticoagulants and bleeding and stroke risk. Methods All AF patients newly prescribed with an oral anticoagulant in the Stockholm Healthcare database (n=2.3 million inhabitants) from July 2011 until 2016 were included and followed for one year or shorter if they stopped claiming oral anticoagulant treatment or had an outcome of interest. Outcomes were severe bleeds and strokes, requiring acute hospital care. During follow-up, patients were considered exposed to antidepressant after claiming a prescription for the duration of the prescription. With a time-varying Cox regression, we assessed the association between antidepressant use and strokes and bleeds, adjusting for confounders (i.e., age, sex, comorbidities, comedication, and year of inclusion). In addition, we performed a propensity score matched analysis to test the robustness of our findings. Results Of the 30,595 patients included after claiming a prescription for a NOAC (n=13,506) or warfarin (n=17,089), 4 303 claimed a prescription for an antidepressant during follow-up. A total of 712 severe bleeds and 551 strokes were recorded in the cohort. Concomitant oral anticoagulant and antidepressant use was associated with increased rates of severe bleeds (4.7 vs 2.7 per 100 person-years) compared to oral anticoagulant treatment without antidepressant use (aHR 1.42, 95% CI: 1.12–1.80), but not significantly associated with increased stroke rates (3.5 vs 2.1 per 100 person-years, aHR 1.23, 95% CI: 0.93–1.62). No significant differences were observed between different oral anticoagulant classes (i.e., warfarin or NOAC) or different antidepressant classes (i.e., SSRI, TCA, or other antidepressant). Additional propensity-score matched analyses yielded similar results but showed a significantly increased risk for stroke (HR: 1.47, 95% CI: 1.08–2.02). Incidence rates of strokes and bleeds Conclusion Concomitant use of an oral anticoagulant and an antidepressant, irrespective of type, is associated with an increased bleeding risk. Increased awareness and a critical consideration for the need of an antidepressant is recommended in this population. Acknowledgement/Funding Swedish Heart Lung Foundation

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

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420923528 ◽

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.

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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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Evaluation of Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in the Oncology Population

Blood ◽

10.1182/blood.v128.22.5026.5026 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5026-5026

Author(s):

Jessica Hedvat ◽

Christina Howlett ◽

James K. McCloskey ◽

Ruchi Jain

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Cancer Patients ◽

Bleeding Episode ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Package Insert ◽

Increased Risk ◽

Clinically Significant ◽

Risk For Bleeding

Abstract INTRODUCTION: Anticoagulant management of cancer-associated thrombosis is challenging since this patient population is concurrently at an increased risk for bleeding. The use of direct oral anticoagulants [(DOACs) dabigatran, rivaroxaban, apixaban] is not recommended for the treatment of venous thromboembolism (VTE) in cancer patients since there is limited data in this patient population. Despite limited evidence for use, DOACs are commonly prescribed due to ease of administration and lack of required laboratory monitoring. The objective of this study was to evaluate the practice and safety patterns of the DOACs when used for VTE treatment in the oncology population at Hackensack University Medical Center (HackensackUMC). METHODS: This study was a retrospective chart review of adult cancer patients treated at HackensackUMC who received dabigatran, rivaroxaban, or apixaban for the treatment of VTE. The protocol was reviewed and approved by the Institutional Review Board. Patients were identified through a computer generated report of the DOACs which included patients on all inpatient adult oncology floors at HackensackUMC from January 2013 to October 2015. Patients were included in this study if they were 18 years of age or older, admitted to an oncology floor, receiving a DOAC for VTE treatment for at least 48 hours, and had active cancer. Patients were excluded from this study if they were receiving hemodialysis or receiving a DOAC exclusively for the indication of atrial fibrillation. The primary outcomes of this study included the percentage of patients who were receiving a DOAC dosage consistent with that of the package insert and the percentage of patients who experienced clinically significant bleeding. The secondary outcomes of this study included the percentage of patients who had their DOAC held for thrombocytopenia and high risk procedures. Descriptive statistics were used to analyze study outcomes. RESULTS: Of the 126 patients screened, 39 patients were included. Thirty-five patients were on rivaroxaban and 4 patients were on apixaban (Table 1). Ten of 39 patients (26%) were not receiving a DOAC dosage consistent with that of the package insert. Of these 10 patients identified, the majority were receiving a lower DOAC dose than is recommended in the package insert. Our assumption is that these patients received a lower than recommended dose due to concerns for increased risk of bleeding. No patients experienced clinically significant bleeding. Four of 39 patients (10%) experienced a minor bleeding episode, all of which were gastrointestinal and/or genitourinary bleeds (Table 2). Four of 14 thrombocytopenic patients (29%) did not have their DOAC dose held for thrombocytopenia (none of which experienced a bleeding episode). All patients had their DOACs appropriately held for all procedures. CONCLUSION: Increased education and awareness on manufacturer recommended dosing of DOACs is warranted for oncology prescribers. Despite the increased risk for bleeding in cancer patients, no clinically significant bleeding events were identified in our patient cohort. To our knowledge, this is the first study to evaluate the use of DOACs for VTE treatment in patients with cancer at a high risk for bleeding. This data suggests that the use of DOACs may be safe to use for VTE treatment in the oncology population. This study may provide foundation for larger, randomized, controlled trials to determine whether DOACs should be used for VTE treatment in cancer patients. Disclosures Howlett: Eisai: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Sandoz: Honoraria; Teva: Speakers Bureau. McCloskey:Ariad: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau.

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Use of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Comparison of the International Guidelines

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.715878 ◽

2021 ◽

Vol 8 ◽

Author(s):

Daniele Pastori ◽

Danilo Menichelli ◽

Vittoria Cammisotto ◽

Pasquale Pignatelli

Keyword(s):

Systematic Review ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Case Series ◽

British Society ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Serious Adverse Events ◽

First Choice

Antiphospholipid antibody syndrome (APS) requires long-term anticoagulation to prevent recurrent thrombosis. Direct oral anticoagulants (DOACs) have been increasingly used in APS patients, but contradictory guidelines recommendations on their use do exist. We performed a systematic review of literature including studies investigating the role of DOACs in APS patients. At this aim, PubMed and Cochrane databases were searched according to PRISMA guidelines. We identified 14 studies which investigated the use of DOACs in patients with APS, of which 3 randomized clinical trials (RCTs), 1 post-hoc analysis of 3 RCTs, 7 case series and 3 cohort studies (2 prospective and 1 retrospective). Among DOACs, rivaroxaban was the most used (n = 531), followed by dabigatran (n = 90) and apixaban (n = 46). Regarding guidelines indications, the 2019 European Society of Cardiology (ESC) and American Society of Hematology (ASH) guidelines recommend against the use of DOACs in all APS patients. The European League Against Rheumatism (EULAR), British Society for Haematology (BSH), and International Society on Thrombosis and Haemostasis (ISTH) guidance provided more detailed indications stating that warfarin should be the first-choice treatment but DOACs may be considered in patients (1) already on a stable anticoagulation with a DOAC, (2) with low-quality anticoagulation by warfarin, (3) unwilling/unable to undergo INR monitoring, (4) with contraindications or serious adverse events under warfarin. Patients with arterial APS or triple positivity should be treated with warfarin while venous APS with single or double positivity may be candidate to DOACs, but high-quality studies are needed.

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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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