Secondary Prevention Of Recurrent Venous Thromboembolism Research Articles

Rivaroxaban and the EINSTEIN clinical trial programme.

Rivaroxaban, a direct oral anticoagulant, is widely used for the treatment of venous thromboembolism (VTE) in adult patients. The approval of rivaroxaban for the treatment of deep vein thrombosis and pulmonary embolism and the extended secondary prevention of recurrent VTE is based on the results of the EINSTEIN DVT and EINSTEIN PE trials, and the EINSTEIN EXT and EINSTEIN CHOICE trials, respectively. This review provides an updated overview of these completed EINSTEIN studies in adult patients, including results of subanalyses in patients at high risk of recurrent VTE, and discusses the emerging data from the EINSTEIN Junior programme, which is evaluating the use of rivaroxaban for the treatment of paediatric VTE. In the EINSTEIN DVT and EINSTEIN PE trials, rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily thereafter) was shown to be an effective and safe alternative to standard anticoagulation for the treatment of deep vein thrombosis and pulmonary embolism in a broad range of adult patients. These results are supported by increasing amounts of real-world data from patients treated with rivaroxaban in routine clinical practice worldwide. In the EINSTEIN EXT and EINSTEIN CHOICE trials, rivaroxaban was superior to placebo and acetylsalicylic acid, respectively, for the extended treatment of VTE – physicians can now choose between two doses of rivaroxaban (20 mg once daily or 10 mg once daily) for the extended prevention of recurrent VTE, based on a patient's risk of recurrence, bleeding and personal preferences.

COSIMO \u2013 patients with active cancer changing to rivaroxaban for the treatment and prevention of recurrent venous thromboembolism: a non-interventional study

BackgroundAround 20% of venous thromboembolism (VTE) cases occur in patients with cancer. Current guidelines recommend low molecular weight heparin (LMWH) as the preferred anticoagulant for VTE treatment. However, some guidelines state that vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are acceptable alternatives for long-term therapy in some patients if LMWHs are not available. LMWHs and VKAs have a number of drawbacks that can increase the burden on patients. DOACs, such as rivaroxaban, can ameliorate some burdens and may offer an opportunity to increase patient satisfaction and health-related quality of life (HRQoL). The Cancer-associated thrOmboSIs – patient-reported outcoMes with rivarOxaban (COSIMO) study is designed to provide real-world information on treatment satisfaction in patients with active cancer who switch from LMWH or VKA to rivaroxaban for the treatment of acute VTE or to prevent recurrent VTE.MethodsCOSIMO is a prospective, non-interventional, single-arm cohort study that aims to recruit 500 patients in Europe, Canada and Australia. Adults with active cancer who are switching to rivaroxaban having received LMWH/VKA for the treatment and secondary prevention of recurrent VTE for at least the previous 4 weeks are eligible. Patients will be followed for 6 months. The primary outcome is treatment satisfaction assessed as change in the Anti-Clot Treatment Scale (ACTS) Burdens score at week 4 after enrolment compared with baseline. Secondary outcomes include treatment preferences, measured using a discrete choice experiment, change in ACTS Burdens score at months 3 and 6, and change in HRQoL (assessed using the Functional Assessment of Chronic Illness Therapy – Fatigue questionnaire). COSIMO will collect data on patients’ medical history, patterns of anticoagulant use and incidence of bleeding and thromboembolic events. Study recruitment started in autumn 2016.ConclusionsCOSIMO will provide information on outcomes associated with switching from LMWH or VKA therapy to rivaroxaban for the treatment or secondary prevention of cancer-associated thrombosis in a real-life setting. The key goal is to assess whether there is a change in patient-reported treatment satisfaction. In addition, COSIMO will facilitate the evaluation of the safety and effectiveness of rivaroxaban in preventing recurrent VTE in this patient population.Trial registrationNCT02742623. Registered 19 April 2016.

Outcomes of Venous Thromboembolism (VTE) Treatment in Thrombocytopenic Leukemic Patients

BACKGROUNDThe current standard of care for the treatment of cancer-related VTE is low molecular heparin. Treatment of VTE in leukemia is complicated as patients suffer severe thrombocytopenia during the different phases of their malignant disease. The optimal treatment of cancer-related VTE in this population has still not been widely studied. Therefore, there is a dire need for research to provide evidence-based guidance on the optimal management of cancer related-VTE in leukemia population.OBJECTIVESThe primary objective of the study was to estimate the recurrence rate of VTE (proximal lower extremity, pulmonary embolism or both) at 6 months from the institution of VTE-related treatment. Secondary objectives included overall survival, recurrent VTE event-free survival, and rate of complications attributed to therapies for VTE.METHODSA retrospective chart review of adult patients with thrombocytopenic leukemia patients who suffered VTE and were treated at MD Anderson Cancer Center between January 2002 and March 2016. Demographic, clinical, and VTE treatment-related data were collected. Primary and secondary outcomes were compared among the different VTE treatment-modalities using non-parametric methods. Kaplan-Meier curves were calculated and compared between the groups of VTE-treatment modalities using Log-Rank test. All comparisons were performed with a test significance of 0.05.RESULTS:At the time of abstract submission, a total of 101 patient-data have been analyzed. The most common type of leukemia was AML (2/3 of all cases). Study outcomes were compared between three groups: anticoagulation only, inferior vena cava filter only and no VTE-treatment intervention. We found no statistically significant differences in the demographic and clinical characteristics between the three groups, except for a lower median platelet count in the patients in whom no VTE-treatment intervention was performed (p<0.05). The VTE recurrence rate was low (<5%) and not different between the intervention groups. The median overall survival of the general population was poor (< 6 months) and significantly worse in patients who did not receive anticoagulation therapy for the management of VTE (p<0.01).CONCLUSION:Our study is the largest cohort reported to date on management of VTE in thrombocytopenic leukemia patients. Our preliminary data indicated that anticoagulation therapy and non-pharmacologic interventions for the management of VTE seemed to be safe and equivalent for the secondary prevention of recurrent VTE in that population. Future prospective cohort studies will likely confirm these findings. DisclosuresNo relevant conflicts of interest to declare.

Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants.

Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE). For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling.

Clinical use of rivaroxaban: pharmacokinetic and pharmacodynamic rationale for dosing regimens in different indications.

Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily dose is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery, the long-term prevention of stroke in patients with non-valvular atrial fibrillation, and the long-term secondary prevention of recurrent VTE. Twice-daily dosing is required in the acute phase of treatment in patients with VTE and in the combination of rivaroxaban with standard single or dual antiplatelet therapy for secondary prevention after acute coronary syndrome events. This article reviews the empirical and clinical rationale supporting the dose regimens of rivaroxaban in each clinical setting.

Pharmacokinetic and pharmacodynamic evaluation of rivaroxaban: considerations for the treatment of venous thromboembolism.

Patients with deep vein thrombosis or pulmonary embolism are recommended to receive anticoagulation for acute treatment and secondary prevention of venous thromboembolism (VTE). Fast-acting direct oral anticoagulants, with or without parenteral heparin, have the potential to replace vitamin K antagonists in this setting. Rivaroxaban, a direct Factor Xa inhibitor, is approved in the European Union and the United States for the single-drug treatment of deep vein thrombosis and pulmonary embolism and the secondary prevention of recurrent VTE in adults. The approved rivaroxaban dose schedule (15 mg twice daily for 3 weeks followed by 20 mg once daily) was derived based on pharmacological data from the clinical development programme to achieve a strong antithrombotic effect in the acute treatment phase and address the need to balance efficacy and bleeding risk for long-term treatment with a once-daily dose in the maintenance phase. Data from dose-ranging studies, pharmacokinetic modelling and randomised phase III trials support the use of this regimen. Other direct oral anticoagulants have also shown favourable efficacy and safety compared with standard treatment, and apixaban (European Union) and dabigatran (European Union and United States) have been approved in this indication. There are practical aspects to rivaroxaban use that must be considered, such as treatment of patients with renal and hepatic impairment, drug–drug interactions, monitoring of effect and management of bleeding. This review discusses the derivation of the VTE treatment regimen for rivaroxaban, summarises the clinical data for rivaroxaban and other direct oral anticoagulants in VTE treatment, and considers the practical aspects of rivaroxaban use in this setting.

Renaissance of Aspirin for the Primary and Secondary Prevention of Venous Thromboembolism

Long-standing controversy has surrounded aspirin as an antithrombotic modality to prevent venous thromboembolism (VTE), particularly in the orthopedic surgery arena. New data are emerging on the use of aspirin for both primary VTE prevention and secondary prevention of recurrent VTE after an initial anticoagulation course. This review article will provide the history behind the controversy, information regarding recent or ongoing clinical trials of aspirin for primary VTE prevention in major orthopedic surgery, evidence for aspirin in secondary prevention of recurrent VTE, and suggestions for future research. Aspirin may be a reasonable option for VTE prevention in certain major orthopedic surgery patients. Additionally, investigation among non-orthopedic populations such as the acutely ill medical patient and the non-orthopedic surgery patient is encouraged to provide further safety and efficacy data.