edoxaban and Neoplasms

Direct oral anticoagulants (DOACs) offer an alternative to low-molecular-weight heparin (LMWH) and warfarin for treating cancer-associated thrombosis (CAT).. To determine the cost and effectiveness of DOACs versus LMWH.. Cohort-state transition decision analytic model.. Network meta-analysis comparing DOACs versus LMWH.. Adult patients with cancer at the time they develop thrombosis.. Lifetime.. Health care sector.. Strategies of 1) enoxaparin, 2) apixaban, 3) edoxaban, and 4) rivaroxaban for treatment of CAT.. Incremental cost-effectiveness ratio (ICER) in 2022 U.S. dollars per quality-adjusted life-year (QALY) gained.. In the base-case scenario, using drug prices from the U.S. Department of Veterans Affairs Federal Supply Schedule, apixaban dominated enoxaparin and edoxaban by being less costly and more effective. Rivaroxaban was slightly more effective than apixaban, with an ICER of $493 246. In a scenario analysis using "real-world" drug prices from GoodRx, rivaroxaban was cost-effective with an ICER of $50 053 per QALY.. Results were highly sensitive to monthly drug costs. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of $50 000 per QALY, apixaban was preferred in 80% of simulations. However, sensitivity analyses also demonstrated that apixaban only remained cost-effective if monthly medication costs were below $530. Above this, rivaroxaban became cost-effective.. An assumption was made that patients would continue anticoagulation indefinitely unless they suffered a major bleed. Nonmedical costs such as patient and caregiver loss of productivity were not accounted for, and long-term thrombotic complications were not explicitly modeled.. The 3 DOACs are more effective and more cost-effective than LMWH. The most cost-effective DOAC depends on the relative cost of each of these agents. These are important considerations for treating physicians and health policymakers.. None.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Enoxaparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Quality-Adjusted Life Years; Rivaroxaban; Thrombosis

Direct oral anticoagulants (DOACs) are increasingly being used for the treatment of cancer-associated venous thromboembolism (CAT). However, there is limited evidence of the efficacy of DOACs for the treatment of gynecological CAT. Thus, this study aimed to investigate the efficacy and safety of edoxaban for the treatment of gynecological CAT using Japanese real-world data.. We reviewed the medical records of patients with 371 gynecological cancer who received edoxaban or vitamin K antagonist (VKA) between January 2011 and December 2018.. Altogether, 211 and 160 patients were treated with edoxaban and VKA, respectively. Fourteen patients (6.8%) in the edoxaban group and 22 (13.8%) in the VKA group showed recurrence of venous thromboembolism (VTE). Cumulative VTE recurrence was not significantly different between the 2 groups (p=0.340). Adverse events occurred in 15 (7.1%) and 11 (6.9%) patients in the edoxaban and VKA groups, respectively (p=0.697). Subgroup analysis of the edoxaban and VKA groups according to different tumor types, including ovarian, endometrial, and cervical cancer, showed equivalent outcomes in terms of VTE recurrence and adverse events. Patients without pulmonary embolism (PE) were mostly omitted from initial unfractionated heparin (UFH) therapy prior to administration of edoxaban. However, this did not increase the recurrence of VTE.. This study confirmed that edoxaban is effective and safe for the treatment of gynecological CAT. This finding was consistent for different types of gynecological cancer. Additionally, initial UFH therapy prior to the administration of edoxaban may be unnecessary for patients without PE.

Topics: Administration, Oral; Anticoagulants; Heparin; Humans; Japan; Neoplasms; Pulmonary Embolism; Pyridines; Thiazoles; Venous Thromboembolism

Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15-25% of all VTE cases. For decades, the standard treatment for CAT used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score ≥2 prior to starting new chemotherapy, low bleeding risk, no interfering medications).

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear.. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA).. We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8).. For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer. Moreover, management of VTE is frequently connected with complications, namely risk of recurrent VTE and bleeding. Low molecular weight heparins (LMWH) therapy administrated for 3-6 months is currently considered a standard for the treatment of cancer-associated VTE (CA-VTE). Direct oral factor Xa inhibitors (FXaI) apixaban, edoxaban and rivaroxaban have emerged as a new possibility for long-term antithrombotic therapy for VTE. These agents expose several advantages in individuals with cancer, and might overcome several disadvantages connected with LMWH therapy.. First clinical studies with oral FXaI for the treatment of CA-VTE with very promising results were recently published. The article summarizes current data regarding the use of oral FXaI in the treatment of CA-VTE.

Topics: Administration, Oral; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Venous Thromboembolism

Direct oral anticoagulants, anti-IIa or anti-Xa, are widely used in the treatment and prevention of venous thromboembolic disease as well as in nonvalvular atrial fibrillation. Direct oral anticoagulants are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, theoretical drug interactions exist since direct oral anticoagulants are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway. Direct oral anticoagulants do not have a marketing authorization for the treatment of cancer-associated thrombosis unlike low-molecular-weight heparins which remain the gold standard treatment today. However, recent studies have compared low-molecular-weight heparins to direct oral anticoagulants in the treatment of cancer-associated thrombosis. Results of these studies showed a non-inferiority of direct oral anticoagulants in the prevention of recurrent thromboembolic events but at the cost of an increased hemorrhagic risk, in particular for patients with gastrointestinal and urogenital cancers. Thus, international guidelines, unlike French guidelines, integrate them in first line of the therapeutic strategy of cancer patients. We are certainly entering an era of personalized therapy for cancer-associated thrombosis, considering cancer type and also the theoretical risk of drug interactions with anti-cancer treatments or supportive care.

Topics: Anticoagulants; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Cytochrome P-450 Enzyme System; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasm Proteins; Neoplasms; Pyrazoles; Pyridines; Pyridones; Recurrence; Rivaroxaban; Secondary Prevention; Thiazoles; Thrombosis; Venous Thromboembolism

Cancer-associated venous thromboembolism remains an important but challenging aspect in the treatment of patients with cancer. Recently, alternatives to injection of low-molecular-weight heparin (LMWH) have been introduced, the non-vitamin K antagonist oral anticoagulants (NOACs), which could potentially alleviate patients from burdensome daily injections.. This review discusses the available evidence exploring the role of NOACs in the treatment and secondary prevention of cancer-associated venous thromboembolism, from randomized trials, observational data, contemporary guideline recommendations, and patient perspectives.. Edoxaban, rivaroxaban, and apixaban have proven attractive alternatives to LMWH for the treatment of cancer-associated venous thromboembolism. Contemporary guidelines have promptly endorsed the use of NOACs in patients with most cancer types. Nonetheless, issues remain regarding bleeding risk, interactions with medical cancer treatment, and the effectiveness and safety for extended treatment periods. There are head-to-head comparisons of the NOACs, and therefore no data favoring the use of one NOAC over the others. Patient's preferences are highly diverse and should be part of routine considerations when weighing risks and benefits associated with various available anticoagulant drugs.

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism

The use of direct oral anticoagulants (DOACs) has been largely -implemented in the management of venous thromboembolic disease in non-cancer patients. In cancer-associated thrombosis, low molecular weight heparins (LMWHs) and especially dalteparin have long been the reference standard therapy. Following the publication of two randomised trials comparing edoxaban and rivaroxaban to -dalteparin, DOACs now represent an alternative with an interesting efficacy and safety profile. Moreover, they offer the comfort of an oral administration and a lower cost. In patients with gastrointestinal or genitourinary cancers however, a higher bleeding risk has been shown with DOACs. LMWHs thus remain the treatment of choice in this group of patients.. L’utilisation des anticoagulants oraux directs (ACOD) pour le traitement de la maladie thromboembolique veineuse (MTEV) chez les patients sans cancer est déjà largement implémentée. En cas de MTEV liée au cancer, les héparines de bas poids moléculaire (HBPM) et en particulier la daltéparine, ont longtemps ­représenté le traitement de référence. Suite à la publication de deux études randomisées récentes comparant l’édoxaban et le rivaroxaban à la daltéparine, les ACOD se sont révélés être une alternative efficace, avec un profil de sécurité satisfaisant, ­offrant par ailleurs le confort d’une administration orale et un coût moindre. Toutefois, en raison d’un risque hémorragique ­accru sous ACOD chez les patients avec un cancer de localisation digestive ou urogénitale, les HBPM restent le traitement de choix dans ce groupe de patients.

Topics: Administration, Oral; Anticoagulants; Dalteparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridines; Rivaroxaban; Thiazoles; Venous Thromboembolism

Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer and anticoagulant treatment in these patients has remained a challenge. Cancer patients with VTE are at increased risk of developing recurrent VTE compared to patients without cancer, but also have a higher risk of major bleeding. In these patients, low molecular weight heparins (LMWHs) have been shown to be more effective and as safe as vitamin K-antagonists (VKAs) for the treatment of VTE. Therefore, the majority of current clinical guidelines recommend LMWHs as the treatment of choice for cancer-associated VTE. However, several issues should be considered regarding the use of LMWHs as daily subcutaneous injections, the costs or risk of heparin-induced thrombocytopenia. In recent years, direct-acting oral anticoagulants (DOACs) have shown similar efficacy and better safety profile compared to VKAs and have become the standard of care for the treatment of VTE in the general population. Because DOACs offer a simple oral treatment regimen without the need for anticoagulation control, they could be an attractive alternative to LMWH. Before DOACs become an accepted treatment option for cancer associated VTE, they have to be evaluated in a head-to-head comparison with LMWH. Data from two randomized trials comparing DOACs vs. LMWH have recently been published. In the present review, we will provide three clinically relevant questions on the use of DOACs in patients with cancer and VTE and provide an overview on recent evidence on this topic: 1) are DOACs a treatment option for the prevention of VTE in cancer patients?; 2) what is the place for DOACs in patients with cancer-associated VTE?; 3) should I use DOACs for the extended treatment of cancer-related VTE?.

Topics: Anticoagulants; Clinical Trials as Topic; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridines; Rivaroxaban; Thiazoles; Venous Thromboembolism

Cancer accounts for 20% of all venous thromboembolism (VTE) worldwide and cancer patients are at four- to sevenfold increased risk of thrombosis compared to non-cancer patients. VTE is also a morbid complication of cancer and its incidence is rising. Thrombosis is also a second leading cause of death in cancer patients. The standard of care management for the prevention and treatment of cancer-associated thrombosis (CAT) remains the administration of low-molecular-weight heparins (LMWHs). In the last decade, five direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban, have been approved for the treatment and prevention of VTE in the general patient population. In this review, we discuss the results of the already published clinical trials with DOACs in the treatment of CAT and the ongoing clinical trials with DOACs in the prevention and treatment of CAT.

Topics: Administration, Oral; Anticoagulants; Benzamides; Dabigatran; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism

Cancer patients with cancer-associated thrombosis (CAT) are at an elevated risk of recurrent venous thromboembolism (VTE) and of major bleeding while receiving treatment with anticoagulation. Recently, Xa inhibitors have been assessed in cancer patients for the treatment of CAT, providing clinicians and patients with more treatment options.. In this narrative review, the authors evaluate the evidence regarding the efficacy and safety of edoxaban, rivaroxaban, and apixaban in the treatment of CAT.. Xa inhibitors are an effective, safe, and convenient option for the treatment of CAT. Overall, they may be associated with a lower risk of recurrent VTE in cancer patients. Certain subgroups of cancer patients may be at increased risk of major bleeding while on treatment with Xa inhibitors, when compared to low-molecular-weight-heparin (LMWH). The current published data suggests an increase in gastrointestinal (GI) major bleeding in patients with GI malignancies. Other patient, treatment, and cancer characteristics may also be associated with a higher risk of major bleeding. Therefore, when assessing the appropriateness of Xa inhibitors for the treatment of CAT, the clinician must take into consideration the known interactions of these drugs, the individualized bleeding risk, and the patient's preferences, in order to make the best possible anticoagulation therapy recommendation.

Topics: Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

While trials have demonstrated non-inferiority of direct oral anticoagulant drugs (DOAC) to low-molecular-weight heparins (LMWH) for the treatment of cancer associated thrombosis (CAT), it is unclear if the newer intervention is cost-effective.. We performed a cost-utility analysis using a Markov state-transition model over a time horizon of 60 months in a hypothetical cohort of 65-year-old patients with active malignancy and first acute symptomatic CAT who were eligible to receive either rivaroxaban/edoxaban or dalteparin. We obtained transition probability, relative risk, cost, and utility inputs from the literature. We estimated the differential impact on costs and quality-adjusted life years (QALYs) per patient and performed one-way and probabilistic sensitivity analyses to test the robustness of results.. Using the base-case analysis over 60 months, DOAC versus dalteparin was associated with an incremental cost reduction of $24,129 with an incremental QALY reduction of 0.04. In the one-way sensitivity analysis, the cost of dalteparin contributed the most to the incremental cost difference; relative risk of death related to underlying cancer contributed the most of the incremental QALY difference. The probabilistic sensitivity analysis confirmed the base-case analysis, with a large reduction in cost but small reduction in QALYs.. Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.

Topics: Anticoagulants; Cost-Benefit Analysis; Dalteparin; Factor Xa Inhibitors; Humans; Neoplasms; Pyridines; Quality-Adjusted Life Years; Rivaroxaban; Thiazoles; Thrombosis

Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Topics: Ambulatory Care; Anticoagulants; Dabigatran; Female; Hemorrhage; Humans; Length of Stay; Male; Neoplasms; Patient Discharge; Patient Selection; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Severity of Illness Index; Substance Abuse, Intravenous; Thiazoles

Direct oral anticoagulants (DOACs) were developed to compensate for the demerits of warfarin. In Japan, three factor Xa inhibitors are used for the treatment of venous thromboembolism (VTE): edoxaban, rivaroxaban, and apixaban. Despite problems, such as the inability to monitor their effect and the lack of an antidote, these inhibitors have the same efficacy as conventional treatment with warfarin, and they are associated with a significantly high degree of safety in relation to hemorrhagic complications. East Asians, including Japanese, suffer from hemorrhage more frequently; therefore, DOACs are considered to be highly effective. Although there is no evidence to date, DOACs may be effective in a wide variety of ways, including the possibility that they prevent recurrence over the long term, reduce the length of hospitalization, allow treatment to be started on an outpatient basis, and be effective in cancer patients.

Topics: Administration, Oral; Anticoagulants; Clinical Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Hospitalization; Humans; Japan; Neoplasms; Outpatients; Platelet Count; Pyrazoles; Pyridines; Pyridones; Recurrence; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

Cancer 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 long-term 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.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism

New oral anticoagulants (NOACs) are likely to have a major impact in the next few years, changing clinical practice of anticoagulation therapy. Evidence on its efficacy and superiority to vitamin K antagonists (VKAs) in treating non-cancer patients have been reported in a few clinical trials. However, patients with cancer are complicated by the prothrombotic nature of the disease, need for potentially invasive surgery and interventions, and altered drug handling. This chapter examines the available evidence and guidelines on the use of NOAC in patients with cancer.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Catheters, Indwelling; Dabigatran; Drug Administration Schedule; Drug Dosage Calculations; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) is a common complication of cancer and has a significant impact on morbidity and mortality in patients with malignancies. Low molecular weight heparins (LMWHs) currently represent the drug of choice for both initial and long-term treatment of cancer-associated thrombosis. In recent years, however, a new class of novel oral anticoagulants (NOACs) inhibiting directly thrombin or activated factor X have been proposed as an alternative therapeutic option on the basis the results of subgroup analyses of phase III randomized controlled trials, including few cases of patients with cancer. After analysis of the available literature data, we conclude that although potentially interesting, future research specifically conducted in cancer patients is needed to clarify the role of these newer anticoagulant agents in prevention and treatment of cancer-related VTE.

Topics: Administration, Oral; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridines; Randomized Controlled Trials as Topic; Recurrence; Thiazoles; Thrombin; Venous Thromboembolism

For decades the antithrombotic management of venous thromboembolism (VTE) was limited to parenteral heparin formulations and oral vitamin K antagonists. Even though both classes of anticoagulants are effective, they have several limitations, including a narrow therapeutic window and the need to monitor anticoagulant activity. Direct oral anticoagulants (DOACs) that specifically target factor IIa or Xa have emerged. Recent data suggest that they are at least as effective and as safe as conventional therapy and have practical advantages, such as fixed dose regimen and no need for laboratory monitoring. Hence, they represent a major step forward in the acute treatment and long-term prevention of VTE. In this review, we outline the use of DOACs in the management of VTE and provide an overview of recently published major trials.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism

The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding.. In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point.. From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point.. In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death.. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

Topics: Aged; Anticoagulants; Female; Hemorrhage; Humans; Male; Neoplasms; Thrombosis; Venous Thromboembolism; Venous Thrombosis

Patients with active cancer and venous thromboembolism (VTE) are at high risk of recurrence. Therefore, continued anticoagulant therapy beyond the initial 6 months is suggested in this patient population, but evidence supporting this approach is limited.. The Hokusai VTE Cancer trial compared edoxaban with dalteparin for VTE treatment in patients with active cancer. This post hoc analysis focused on the follow-up period from 6 to 12 months. The primary outcome was the composite of adjudicated first recurrent VTE or major bleeding. Secondary outcomes included recurrent VTE, major bleeding, and clinically relevant bleeding.. Of the 522 and 524 patients randomized to edoxaban or dalteparin, 294 (56%) received edoxaban and 273 (52%) received dalteparin for more than 6 months (median duration of 318 and 211 days, respectively). Between 6 and 12 months, the primary outcome during study treatment occurred in seven patients (2.4%) in the edoxaban group and six patients (2.2%) in the dalteparin group (unadjusted hazard ratio 1.05; 95% confidence interval, 0.36-3.05). Recurrent VTE occurred in two patients (0.7%) in the edoxaban group and in three patients (1.1%) in the dalteparin group, whereas major bleeding occurred in 5 (1.7%) and three patients (1.1%), respectively.. The rates of recurrent VTE or major bleeding are relatively low among patients with active cancer receiving extended anticoagulant therapy beyond 6 months. Extended treatment with oral edoxaban appears as effective and safe as subcutaneous dalteparin.

Topics: Aged; Blood Coagulation; Dalteparin; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Neoplasms; Prospective Studies; Pulmonary Embolism; Pyridines; Recurrence; Risk Factors; Thiazoles; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear.. In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration.. Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P=0.006 for noninferiority; P=0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6).. Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials.gov number, NCT02073682 .).

Topics: Adult; Aged; Anticoagulants; Dalteparin; Follow-Up Studies; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Pyridines; Recurrence; Thiazoles; Venous Thromboembolism

Cancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of major bleeding events were classified into four categories of increasing severity. A one-stage meta-analysis was used to evaluate the effect of cancer on the severity of the clinical presentation and course by estimating crude odds ratios (ORs) and ORs adjusted for age, sex and anticoagulant type with 95% confidence intervals (CIs). The study group comprised 290 patients with major bleeding, of whom 50 (17%) had cancer. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR, 0.90; 95% CI, 0.47-1.72). The clinical course was found to be severe in 20 and 25% of patients with and without cancer, respectively (adjusted OR, 0.75; 95% CI, 0.35-1.61). The present study suggests that the clinical presentation and course of anticoagulant-related major bleeding events are not more severe in cancer patients than in patients without cancer. This may be reassuring for physicians who treat cancer patients with anticoagulant-related bleeding.

Topics: Aged; Anticoagulants; Blood Transfusion; Double-Blind Method; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Prospective Studies; Pyridines; Rivaroxaban; Thiazoles; Venous Thromboembolism

In the Hokusai VTE Cancer study, edoxaban was non-inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer-associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1-4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days); no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9%) and 11 (2.1%) patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub-group occurred in 5 of 165 (3.0%) and in 3 of 140 (2.1%) patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer-associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit-risk weighting.

Topics: Aged; Anticoagulants; Clinical Decision-Making; Dalteparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Patient Selection; Pyridines; Recurrence; Risk Assessment; Risk Factors; Severity of Illness Index; Thiazoles; Time Factors; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism occurs commonly in patients with cancer. Direct oral anticoagulants are non-inferior to conventional anticoagulants for the treatment of venous thromboembolism. We hypothesised that edoxaban, a direct oral inhibitor of activated clotting factor Xa, might be more suitable than conventional anticoagulants in the management of cancer-associated venous thromboembolism. The aim of this study was to assess the efficacy and safety of edoxaban compared with warfarin in a subgroup of patients with cancer enrolled in the Hokusai-VTE trial.. We did a prespecified subgroup analysis in August, 2013, and a post-hoc analysis of non-inferiority and safety in March, 2016, of the patients with cancer enrolled in the randomised, double-blind, double-dummy, multicentre, Hokusai-VTE trial done between Jan 28, 2010, and Oct 31, 2012. In this study, patients aged at least 18 years with acute symptomatic deep-vein thrombosis or acute symptomatic pulmonary embolism (with or without deep-vein thrombosis) were assigned to receive edoxaban 60 mg once per day (or 30 mg once per day for patients with a creatinine clearance of 30-50 mL/min, bodyweight <60 kg, or who were receiving concomitant treatment with the P-glycoprotein inhibitors quinidine or verapamil) or warfarin (dose adjusted to maintain the international normalised ratio between 2·0 and 3·0) or placebos for either group for at least 3 months up to 12 months. All patients received initial therapy with open-label enoxaparin or unfractionated heparin for at least 5 days. Edoxoban (or placebo) was started after discontinuation of initial heparin; warfarin (or placebo) started concurrently with the study regimen of heparin. In our analysis we examined data for a subgroup of these patients who had a history of cancer or who had been categorised as having active cancer by the study physician at the time of enrolment. Additionally, all patients with a history of cancer were reviewed post hoc and categorised according to the presence or absence of active cancer. The primary efficacy outcome was the proportion of these patients with symptomatic recurrent venous thromboembolism during the 12-month study period, analysed in the modified intention-to-treat population, with an upper limit of the CI for the hazard ratio (HR) of 1·5. The principal safety outcome was the proportion of patients who had clinically relevant bleeding in the population of patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT00986154.. Of 771 patients with cancer enrolled in the trial, 378 were assigned to edoxaban and 393 to warfarin. Recurrent venous thromboembolism occurred in 14 (4%) of 378 patients given edoxaban and in 28 (7%) of 393 patients given warfarin (hazard ratio [HR] 0·53, 95% CI 0·28-1·00; p=0·0007). The upper limit of this 95% CI did not exceed the non-inferiority margin of 1·5 that was prespecified for the trial. Clinically relevant bleeding (major or non-major) occurred in 47 (12%) of 378 patients who received edoxaban and in 74 (19%) of 393 patients who received warfarin; HR for clinically relevant bleeding 0·64, 95% CI 0·45-0·92; p=0·017. Major bleeding occurred in ten (3%) of 378 patients with a history of cancer who received edoxaban and in 13 (3%) of 393 who received warfarin (HR 0·80, 95% CI 0·35-1·83).. Edoxaban might be as effective as warfarin for the treatment of patients with cancer with venous thromboembolism, and with less clinically relevant bleeding. Additional clinical trials of edoxaban versus low-molecular-weight heparin for the treatment of venous thromboembolism in patients with cancer are warranted.. Daiichi Sankyo.

Topics: Aged; Double-Blind Method; Equivalence Trials as Topic; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Prognosis; Pyridines; Survival Rate; Thiazoles; Venous Thromboembolism

Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism (VTE) in cancer patients, but they have not been compared with low-molecular-weight heparin (LMWH), the current recommended treatment for these patients. The Hokusai VTE-cancer study is a randomised, open-label, clinical trial to evaluate whether edoxaban, an oral factor Xa inhibitor, is non-inferior to LMWH for treatment of VTE in patients with cancer. We present the rationale and some design features of the study. One such feature is the composite primary outcome of recurrent VTE and major bleeding during a 12-month study period. These two complications occur frequently in cancer patients receiving anticoagulant treatment and have a significant impact. The evaluation beyond six months will fill the current gap in the evidence base for the long-term treatment of these patients. Based on the observation that the risk of recurrent VTE in patients with active cancer is similar to that in those with a history of cancer, the Hokusai VTE-cancer study will enrol patients if whose cancer was diagnosed within the past two years. In addition, patients with incidental VTE are eligible because their risk of recurrent VTE is similar to that in patients with symptomatic disease. The unique design features of the Hokusai VTE-cancer study should lead to enrolment of a broad spectrum of cancer patients with VTE who could benefit from oral anticoagulant treatment.

Topics: Adult; Anticoagulants; Dalteparin; Double-Blind Method; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Prospective Studies; Pulmonary Embolism; Pyridines; Recurrence; Research Design; Sample Size; Thiazoles; Time Factors; Treatment Outcome; Venous Thrombosis

The increased risk of thrombosis and bleeding with an active tumor disease is known as the so-called "thrombo-hemorrhagic syndrome", which places high demands on anticoagulation. There are currently 4 randomized, prospective studies on the use of new, non-vitamin K dependent oral anticoagulants (NOAC) for the treatment of venous thromboembolism (VTE) that have occurred in oncology. The FXa inhibitors rivaroxaban, edoxaban and twice apixaban were each used in individual studies versus the standard therapeutic agent dalteparin. Since there is no direct head-to-head comparison of the FXa inhibitors mentioned within a study, the largest study - always compared to dalteparin - was evaluated for each NOAC. The studies were analyzed with regard to their effectiveness, safety, fatal bleeding rates, the risk of gastrointestinal bleeding (GIB) and other differences using descriptive statistics. With dalteparin, the mean VTE recurrence rate was approximately 9% over a 6-month treatment period. All three FXa inhibitors were not inferior to dalteparin in terms of potency. The VTE recurrence rate was - 2.3% lower in edoxaban and apixaban-treated patients and - 5.0% in rivaroxaban-treated patients. In terms of safety, there was an increased rate of severe bleeding (both + 2.4%) for rivaroxaban and edoxaban compared to dalteparin; in particular, the number of GIBs was significantly increased. In contrast, the number of severe bleeding was not increased for apixaban, as was the case for various bleeding types including GIB. In the Apixaban study, the overall rate of severe GIB, which accounted for about 50% of all severe bleeding, and that of clinically relevant non-severe bleeding, were the lowest. The FXa inhibitors are not inferior to the standard therapy with dalteparin in the VTE recurrence rate in oncological patients. The GIB rate appears to be an important predictive factor for the safety of this group of substances, so that tumor location, gastrointestinal risk factors and other individual criteria should be given greater consideration in future therapy decisions for or against an FXa inhibitor.. Das erhöhte Thrombose- und Blutungsrisiko bei aktiver Tumorerkrankung wird als sog. „thrombo-hämorrhagisches Syndrom“ bezeichnet, welches hohe Anforderungen an die Antikoagulation stellt. Aktuell liegen 4 randomisierte, prospektive Studien zum Einsatz von neuen, nicht Vitamin K-abhängigen oralen Antikoagulantien (NOAK) zur Behandlung von in der Onkologie aufgetretenen venösen Thromboembolien (VTE) vor. Dabei wurden die FXa-Inhibitoren Rivaroxaban, Edoxaban und zweimal Apixaban jeweils in einzelnen Studien gegenüber dem Standardtherapeutikum Dalteparin eingesetzt. Da es keinen direkten Head-to-Head-Vergleich der genannten FXa-Inhibitoren innerhalb einer Studie gibt, wurde zu jedem NOAK die jeweils größte Studie – stets verglichen gegenüber Dalteparin – ausgewertet. Die Studien wurden bzgl. ihrer Wirksamkeit, Sicherheit, fataler Blutungsraten, dem Risiko für gastrointestinale Blutungen (GIB) und sonstiger Unterschiede anhand deskriptiver Statistik analysiert. Unter Dalteparin ergab sich eine mittlere VTE-Rezidivrate von ca. 9% bei einem 6-monatigen Behandlungszeitraum. Alle 3 FXa-Inhibitoren waren gegenüber Dalteparin bezüglich der Wirksamkeit nicht unterlegen. Die VTE-Rezidivrate war bei mit Edoxaban und Apixaban behandelten Patienten um – 2,3% und bei Rivaroxaban um – 5,0% niedriger.Bei der Sicherheit fanden sich – jeweils gegenüber Dalteparin – für Rivaroxaban und Edoxaban eine erhöhte Rate an schweren Blutungen (jeweils +2,4%); insbesondere war hierbei die Zahl GIB deutlich erhöht. Dagegen war für Apixaban die Zahl schwerer Blutungen, wie auch für verschiedene Blutungstypen inkl. GIB, nicht erhöht. In der Apixabanstudie war insgesamt die Rate von schweren GIB, die ca. 50% aller schweren Blutungen ausmachten, und die der klinisch-relevanten nicht schweren Blutungen, am niedrigsten. Die FXa-Inhibitoren sind der Standardtherapie mit Dalteparin in der VTE-Rezidivrate bei onkologischen Patienten nicht unterlegen. Die GIB-Rate scheint ein wichtiger prädiktiver Faktor für die Sicherheit dieser Substanzgruppe zu sein, sodass Tumorlokalisation, gastrointestinale Risikofaktoren und andere individuelle Kriterien in Zukunft stärker bei der Therapieentscheidung für oder gegen einen FXa-Inhibitor berücksichtigt werden sollten.

Topics: Anticoagulants; Dalteparin; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Neoplasms; Prospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Disease Progression; Humans; Neoplasms; Thrombosis; Venous Thromboembolism; Venous Thrombosis

The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.. In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.. A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.. These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Topics: Administration, Oral; Adult; Age Distribution; Aged; Anticoagulants; Asia; Comorbidity; Cross-Sectional Studies; Dabigatran; Diabetes Mellitus; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension; Latin America; Male; Middle Aged; Middle East; Neoplasms; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries

The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and the assessment of the risk-to-benefit ratio of prolonged anticoagulation for patients with pulmonary embolism (PE).Anticoagulation is performed with unfractionated heparin (UFH) in hemodynamically unstable patients and with low molecular weight heparins (LWMH) or fondaparinux in normotensive patients. In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests. LMWH and fondaparinux are preferred over UFH in the initial anticoagulation of PE since they are associated with a lower risk of bleeding.All patients with PE require therapeutic anticoagulation for at least three months. The current 2019 guidelines of the European Society of Cardiology (ESC) recommend that all eligible patients should be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA). In patients with active cancer, Apixaban, Edoxaban and Rivaroxaban are effective alternatives to treatment with LMWH.The decision on the duration of anticoagulation should consider both, the individual risk of PE recurrence and the individual risk of bleeding. The risk for recurrent PE after discontinuation of treatment is related to the features of the index PE event. While patients with a strong transient risk factor have a low risk of recurrence and anticoagulation can be discontinued after three months, patients with strong persistent risk factor (such as active cancer) have a high risk of recurrence and thus should receive anticoagulant treatment of indefinite duration. Given the favourable safety profile of NOACs (especially if a reduced dosage of Apixaban or Rivaroxaban is initiated after at least six months of therapeutic anticoagulation), extended oral anticoagulation of indefinite duration should be considered for all patients with intermediate risk of recurrence.

Topics: Acute Disease; Dalteparin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fibrinolytic Agents; Fondaparinux; Guideline Adherence; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles

Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. In Brazil, even though low-molecular-weight heparin (LMWH) is the gold standard of care for the management of cancer-associated thrombosis (CAT), its cost limits its use and therefore warfarin is commonly prescribed. Direct oral anticoagulants (DOACs), such as edoxaban, have been introduced as an alternative in this setting.. The aim of this study was to compare the cost-effectiveness of edoxaban with LMWH (Model 1) and warfarin (Model 2) to support clinicians and hospitals when choosing an anticoagulant to manage CAT.. Cost-effectiveness analyses were performed using Markov state-transition models over a timeframe of 5 years, in a hypothetical, 64 years-old patients cancer population with an index VTE event. Transition probabilities, costs, quality-adjusted life years (QALYs) and risk reductions were either derived from the literature, estimated or calculated. A willingness-to-pay limit of 3 Gross Domestic Product (GDP) per head was used. Deterministic and probabilistic sensitivity analyses were performed for robustness. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per QALY gained.. Model 1 base case analysis demonstrated dominance of edoxaban compared to LMWH, with an ICER of $5204.46, representing cost saved per QALY lost. In Model 2, edoxaban was associated with a $736.90 cost increase vs. warfarin, with an ICER of $2541.03. Sensitivity analyses confirmed base-case results.. Edoxaban represents a cost-saving alternative to LMWH for the management of CAT and is cost-effective vs. warfarin.

Topics: Anticoagulants; Brazil; Cost-Benefit Analysis; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridines; Quality-Adjusted Life Years; Thiazoles; Thrombosis; Warfarin

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients' demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients' demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p < 0.001). The efficacy and safety of Xa inhibitors as VTE treatment were comparable between cancer and non-cancer patients, and in elderly and non-elderly patients. This suggests that Xa inhibitors may be promising drugs for VTE treatment, irrespective of age and comorbid cancer.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Japan; Lower Extremity; Male; Middle Aged; Neoplasms; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are safe and efficacious when compared to warfarin for patients with venous thromboembolism (VTE). However, bleeding is a major side effect of anticoagulant therapy in VTE patients. Discontinuation of the DOACs associated to adverse events such as bleeding. The HAS-BLED score predicts warfarin-associated hemorrhage. However, little is known about risk factors for DOAC-associated minor bleeding in VTE patients. We aimed to identify risk factors for minor bleeding in VTE patients that were treated with edoxaban, rivaroxaban, or apixaban. We retrospectively evaluated the data of 212 VTE patients who received treatment with a DOAC. The study endpoint was defined as the occurrence of minor bleeding. Logistic regression analysis was used to determine risk factors that were significantly associated with minor bleeding. A total of 36 (17.0%) patients experienced minor bleeding, with rates of 15.7%, 0%, and 21.3% for edoxaban, rivaroxaban, and apixaban, respectively. In the multivariate analysis, bleeding history or predisposition [odds ratio (OR) 6.083, 95% confidence interval (CI) 2.131-17.364, p=0.001] and cancer (OR 6.397, 95% CI 2.858-14.317, p<0.001) were significantly associated with minor bleeding. Bleeding history or predisposition and cancer were the most important risk factors for DOAC-induced minor bleeding in VTE patients in this study. To continue anticoagulant therapy of the DOACs, further management systems by minor bleeding risk factors for patients with VTE will be required.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Severity of Illness Index; Thiazoles; Venous Thromboembolism

Malignancy is a well-established risk factor for venous thromboembolism and while low-molecular-weight heparin therapy has been standard of care for cancer-associated thrombosis for many years, many patients find injection therapy burdensome. The direct oral anticoagulant edoxaban has been shown to be noninferior to dalteparin for the treatment of cancer-associated thrombosis. In a Markov simulation model, edoxaban with 6-month time horizon and a United States societal perspective with 2017 US dollars, edoxaban was the preferred strategy in the general cancer population (6-month cost $6061 with 0.34 quality adjusted life years) and in a subgroup of patients with gastrointestinal malignancy (6-month cost $7227 with 0.34 quality adjusted life years). The incremental cost effectiveness ratio of dalteparin compared to edoxaban was $1,873,535 in the general oncology population and $694,058 in the gastrointestinal malignancy population.

Topics: Anticoagulants; Cost-Benefit Analysis; Dalteparin; Gastrointestinal Neoplasms; Humans; Markov Chains; Models, Theoretical; Neoplasms; Pyridines; Quality-Adjusted Life Years; Thiazoles; Thrombosis; United States

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Dalteparin; Factor Xa Inhibitors; Humans; Neoplasms; Pyridines; Recurrence; Risk Factors; Secondary Prevention; Thiazoles; Treatment Outcome; Venous Thromboembolism

To evaluate the use of direct-acting oral anticoagulants in patients with cancer and venous thromboembolism (VTE) treated at Ochsner Medical Center with the intent of determining the efficacy and safety of these agents.. Patients were identified by a retrospective data extraction of patients treated at Ochsner Medical Center from January 1, 2013, through December 31, 2015. Patients were included for review if they were ≥18 years of age, with a confirmed diagnosis of VTE and active or history of cancer, and if they received dabigatran, apixaban, rivaroxaban, or edoxaban for at least 6 months. The primary objectives were the rate of recurrence of VTE and the incidence of bleeding at 6 months.. Thirty-seven patients were identified. Twelve patients were diagnosed with PE, 21 with DVT, 3 with DVT and PE, and 1 with DVT and superficial vein thrombosis (SVT). Apixaban was used most often (n = 27). No patients experienced a recurrent DVT or PE at 6 months. Two patients experienced adverse effects during treatment.. In this single-center, retrospective, observational study in patients with cancer receiving DOAC therapy, there were no episodes of recurrent VTE and only 2 episodes of clinically significant bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Neoplasms; Pyridines; Thiazoles; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism (VTE) is a frequent and serious complication of cancer. The current guidelines in the USA and Europe recommend low-molecular weight heparin (LMWH) for the treatment of cancer-associated VTE. In Japan, LMWH is not given for the treatment of VTE; instead edoxaban, an oral direct factor Xa inhibitor, was approved for the treatment of VTE in September 2014. However, the efficacy and safety of the factor Xa inhibitor in cancer patients have not been fully elucidated.. Patients' charts were reviewed retrospectively, and 125 VTE patients (61 cancer patients) in whom edoxaban therapy was started between September 2014 and September 2016 were included in this study. Patients' demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and outcomes until February 2017 were examined.. Patients' characteristics, including age, sex, weight, creatinine clearance, and duration of administration of edoxaban were comparable between cancer and non-cancer patients. No parenteral anticoagulant pretreatment before edoxaban was given in 37.5% and 55.7% of non-cancer and cancer patients, respectively. The incidence of pulmonary embolism was also similar in the two groups. The amount of thrombosis decreased ("improved") or disappeared ("normalized") in 89.6% and 94.1%, respectively, of non-cancer and cancer patients who underwent at least two imaging tests. The frequencies of recurrence of VTE and clinically relevant bleeding were not significantly different between the two groups (p=0.414 and 0.516, respectively). However, 21 cancer patients died, 17 of whom died of cancer, while none of the non-cancer patients died.. The present study showed that the efficacy and safety of edoxaban for the treatment of VTE is comparable between cancer and non-cancer patients. Edoxaban may be a clinically useful therapy for VTE in Japanese cancer patients.

Topics: Aged; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Pyridines; Recurrence; Retrospective Studies; Thiazoles; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Neoplasms; Pyridines; Thiazoles; Venous Thromboembolism

Topics: Humans; Neoplasms; Pyridines; Thiazoles; Venous Thromboembolism

Topics: Humans; Neoplasms; Pyridines; Thiazoles; Venous Thromboembolism

Topics: Humans; Neoplasms; Pyridines; Thiazoles; Venous Thromboembolism

Topics: Humans; Neoplasms; Pyridines; Thiazoles; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Antithrombins; Dabigatran; Dalteparin; Factor Xa Inhibitors; Hemorrhage; Humans; Multicenter Studies as Topic; Neoplasms; Observational Studies as Topic; Patient Acceptance of Health Care; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Most clinical practice guidelines recommend low molecular weight heparin for the treatment of venous thromboembolism (VTE) in cancer patients. In the Hokusai VTE Cancer study, 1050 patients with cancer and acute VTE were randomized to oral edoxaban or subcutaneous dalteparin for at least 6 months and up to 12 months. Edoxaban was non-inferior to dalteparin with respect to the composite outcome of recurrent VTE and major bleeding. The rate of recurrent VTE was numerically lower, but the rate of major bleeding was significantly higher with edoxaban. The frequency of severe major bleeding was similar with edoxaban and dalteparin. The difference in major bleeding was mainly driven by a higher rate of upper gastrointestinal bleeding with edoxaban, especially in patients with gastrointestinal cancer. The pilot Select-D study randomized 406 patients with cancer and VTE to rivaroxaban or dalteparin for 6 months. Recurrent VTE was reduced, while both major and clinically relevant non major bleeding were significantly increased with rivaroxaban. Bleeding mostly involved the gastrointestinal tract and occurred in patients with gastroesophageal cancer. While waiting for ongoing studies on direct oral anticoagulants, the results of the Hokusai VTE Cancer suggest that edoxaban may represent a valuable alternative to low molecular weight heparin for the treatment of cancer-associated VTE. In patients with gastrointestinal cancer, the use of edoxaban requires careful benefit-risk weighting, taking into consideration patient's preferences.

Topics: Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Practice Guidelines as Topic; Pyridines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism

Advances in cancer therapy have led to a significant improvement of survival in most types of malignancies over the past few decades. As a result, there is a growing population of cancer survivors, expected to reach 18 million people in 2030 in the US and a similar number in Europe. Interestingly, cancer survivor studies have shown that although about half of these patients eventually die of cancer, one third of them actually die of cardiovascular disease. Arrhythmias represent a significant part of cardiovascular complications and atrial fibrillation is the main arrhythmia occurring in cancer patients.Antithrombotic therapy is a challenge: the optimal international normalized ratio (INR) level in patients on therapy with vitamin K antagonists is achieved in only 12% of them; in these patients, direct oral anticoagulants seem to be effective and safe for the prevention of stroke and systemic embolic events compared to warfarin and have similar risk of major bleeding. Among the trials, ENGAGE AF-TIMI 48 provides more data on the efficacy and safety of edoxaban in cancer patients.

Topics: Anticoagulants; Atrial Fibrillation; Cancer Survivors; Cardiovascular Diseases; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; International Normalized Ratio; Neoplasms; Pyridines; Stroke; Thiazoles; Warfarin

Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF - TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230-771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78-3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07-2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83-1.42). Relative outcomes with higher-dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism ( HR , 0.60 [95% CI, 0.31-1.15] for malignancy versus HR , 0.89 [95% CI, 0.76-1.05] for no malignancy; interaction P=0.25) and major bleeding ( HR , 0.98 [95% CI, 0.69-1.40] for malignancy versus HR , 0.79 [95% CI, 0.69-1.05] for no malignancy; interaction P=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher-dose edoxaban versus warfarin in patients with malignancy ( HR , 0.54; 95% CI, 0.31-0.93) compared with no malignancy ( HR , 1.02; 95% CI, 0.88-1.18; interaction P=0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Gastrointestinal Neoplasms; Hemorrhage; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prostatic Neoplasms; Pyridines; Stroke; Thiazoles; Warfarin

Topics: Anticoagulants; Antithrombins; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Perioperative Care; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Double-Blind Method; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridines; Thiazoles; Venous Thromboembolism

Patients with cancer account for 20 % of cases of venous thromboembolism (VTE). Cancer patients are at increased risk for VTE during the entire course of their disease, also in absence of traditional VTE risk factors. Furthermore, patients with VTE and cancer have an estimated risk of bleeding of 15-20 % per year while on anticoagulant treatment. For these reasons, treatment of acute VTE in patients with cancer remains a clinical challenge. In clinical studies, which included about 27,000 patients, new oral anticoagulants (NOACs) have been shown to be as effective and safe as conventional anticoagulation (heparin given with and followed by vitamin K antagonists) for the treatment of VTE. In these studies, 1227 patients with active cancer were enrolled. Preliminary results of subgroup analyses and meta-analyses of randomized clinical trials suggest that NOACs could represent an alternative to conventional anticoagulation in patients with active cancer. Further "ad hoc" studies evaluating the clinical benefit of treatment with NOACs in patients with VTE and cancer are needed.

Topics: Anticoagulants; Dabigatran; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism