https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=10660&context=open_access_pubs

American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism.

Venous thrombo-embolism is the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke. Recently published landmark trials paved the way for significant progress in the management of the disease and provided the evidence for the ESC Pulmonary Embolism (PE) Guidelines 2014 update. Risk stratification strategies for non-high-risk PE continue to evolve, with an increasing emphasis on clinical prediction rules and right ventricular (RV) assessment on computed tomographic pulmonary angiography. In the field of anticoagulation treatment, pharmacogenetic testing for vitamin K antagonists on top of clinical parameters was not found to offer a significant benefit during the initiation phase; on the other hand, dosing based on the patient's clinical data seems superior to fixed loading regimens. The phase 3 trial programme of new oral anticoagulants in the treatment of venous thrombo-embolism has been completed, and the results indicate that these agents are at least as effective and probably cause less major bleeding than currently standard treatment. A multicentre prospective phase 4 trial will determine whether early discharge and out-of-hospital treatment of low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. For intermediate-risk PE defined on the basis of imaging tests and laboratory biomarkers, the bleeding risks of full-dose thrombolytic treatment appear too high to justify its use, unless clinical signs of haemodynamic decompensation appear. Patients in whom PE has resulted in chronic thrombo-embolic pulmonary hypertension and who are not suitable for pulmonary endarterectomy, may be expected to benefit from emerging pharmaceutical and interventional treatment options.

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Management of venous thrombo-embolism: an update

Management of Pulmonary Embolism: An Update.

Editor's Choice - European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis.

https://www.thelancet.com/pdfs/journals/lanhae/PIIS2352-3026(14)70018-3.pdf

Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials

Population studies on the incidence of venous thromboembolism (VTE) in patients with active cancer are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The source population consisted of all patients in the UK Clinical Practice Research Datalink, with additional information on hospitalisation and cause of death, between 2001 and 2011. A cancer-related clinical diagnosis or therapy within the 90 days before or after a VTE constituted an active-cancer-associated VTE. Incidence rates of first VTE among patients with active cancer and incidence rates of recurrent VTE during the 10-year observational period after a first VTE event were estimated. Incidence rates of all-cause mortality and age- and gender-specific mortality were also calculated. There were 6,592 active-cancer-associated VTEs with a total of 112,738 cancer-associated person-years of observation. The incidence rate of first VTE in patients with active cancer was 5.8 (95 % confidence interval 5.7–6.0) per 100 person-years. A first VTE recurrence was observed in 591 patients. The overall incidence rate for recurrence was 9.6 (95 % confidence interval 8.8–10.4) per 100 person-years, with a peak at 22.1 in the first six months. Recurrence rates were similar after initial pulmonary embolism and after initial deep-vein thrombosis. The mortality risk after VTE was considerable, with 64.5 % mortality after one year and 88.1 % after 10 years. VTE in patients with active cancer is common and associated with high recurrence and mortality rates. Efforts are needed to prevent VTE and reduce recurrence, especially in the first year after VTE diagnosis.

Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study.

Contemporary data from population studies on the incidence and complications of venous thromboembolism (VTE) are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The cohort was identified from all patients in the UK Clinical Practice Research Datalink (CPRD) with additional linked information on hospitalisation and cause of death. Between 2001 and 2011, patients with first VTE were identified and the subset without active cancer-related VTE observed for up to 10 years for recurrent VTE. The 10-year cumulative incidence rates (CIR) were derived with adjustment for mortality as a competing risk event. A total of 35,373 first VTE events (12,073 provoked, 16,708 unprovoked and 6592 active cancer-associated VTE) among 26.9 million person-years of observation were identified. The overall incidence rate (IR) of VTE was 131.5 (95% CI, 130.2–132.9) per 100,000 person-years and 107.0 (95% CI, 105.8–108.2) after excluding cancer-associated VTE. DVT was more common in the young and PE was more common in the elderly. VTE recurrence occurred in 3671 (CIR 25.2%). The IR for recurrence peaked in the first six months at around 11 per 100 person years. It levelled out after three years and then remained at around 2 per 100 person years from year 4–10 of follow-up. The IRs for recurrences were particularly high in young men. In conclusion, VTE is common and associated with high recurrence rates. Effort is required to prevent VTE and to reduce recurrences.

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Epidemiology of first and recurrent venous thromboembolism: A population-based cohort study in patients without active cancer

Objective:The phase III EINSTEIN DVT and EINSTEIN PE trials demonstrated the potential of oral rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). The length of initial hospitalization in patients presenting with either symptomatic DVT or PE was assessed using hospitalization records from these trials.Methods:Analyses were carried out in the intention-to-treat population, using non-parametric and parametric statistical methods.Results:Overall, 52% (1781/3434) of EINSTEIN DVT patients and 90% (4328/4821) of EINSTEIN PE patients were admitted to hospital. The proportion of hospitalized patients with a length of stay of five or fewer days receiving rivaroxaban was 54% compared with 31% for enoxaparin/vitamin K antagonist (VKA) in patients with DVT. For patients with PE, the corresponding values were 45% and 33%. Stays of 6–10 days were observed in 29% of rivaroxaban-treated patients compared with 45% of enoxaparin/VKA-treated patients for DVT. For patients with PE...

Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism.

Rivaroxaban, an oral, direct factor Xa inhibitor, has been approved for the treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and PE as a fixed-dose, single-drug regimen that does not require initial heparinisation, routine coagulation monitoring or dose adjustment. This study evaluated patient-reported treatment satisfaction in EINSTEIN DVT--a large, open-label, randomised study that compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy in patients with acute symptomatic DVT without PE. As part of EINSTEIN DVT, a total of 1,472 patients in seven countries were asked to complete a new, validated measure of treatment satisfaction--the Anti-Clot Treatment Scale (ACTS)--at scheduled visits throughout 12 months of treatment. ACTS scores were compared between study groups in the intention-to-treat population. Patients reported greater satisfaction in the rivaroxaban group compared with the enoxaparin/VKA group, with higher mean ACTS scores across visits. Mean ACTS Burdens scores were 55.2 vs 52.6 (p<0.0001) in favour of rivaroxaban, equivalent to a moderate effect size of 0.42. The treatment effect was consistent over time, with the mean score difference ranging from 2.18 (month 2) to 3.18 (month 12). Overall mean ACTS Benefits scores were 11.7 vs 11.5 in favour of rivaroxaban (p=0.006). This was associated with a small overall effect size of 0.12. The improvement in ACTS Benefits for rivaroxaban became apparent at month 2 and subsequent visits. Rivaroxaban results in improved treatment satisfaction compared with enoxaparin/VKA among patients with DVT, particularly in reducing patient-reported anticoagulation burden.

Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis

The Anti-Clot Treatment Scale (ACTS) is a 15-item patient-reported instrument of satisfaction with anticoagulant treatment. It includes a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. Its role in clinical trials and other settings should be supported by evidence that it is both clinically meaningful and scientifically sound. The aim of the study was to evaluate the measurement performance of the ACTS (Dutch, Italian, French, German and English language versions) in patients with venous thromboembolism based on traditional psychometric methods. ACTS Burdens and Benefits scale data from a large clinical trial (EINSTEIN DVT) involving 1336 people with venous thromboembolism were analysed at both the scale and item level. Five key psychometric properties were examined using traditional psychometric methods: acceptability, scaling assumptions, reliability (including internal consistency reliability, test-retest reproducibility); validity (including known groups and discriminant validity); and responsiveness. These methods of examination underpin the US Food and Drug Administration recommendations for patient-reported outcome instrument evaluation. Overall, the 12-item ACTS Burdens scale and 3-item ACTS Benefits scale met the psychometric criteria evaluated at both item and scale levels, with the exception of some relatively minor issues in the Dutch language version, which were just below reliability criteria (i.e. alpha = 0.72, test-retest intraclass correlation = 0.79). A consistent finding from item-level evaluations of aggregate endorsement frequencies and skewness suggested that response scales may be improved by reducing the number of response options from five to four. Both the ACTS Burdens and ACTS Benefits scales consistently satisfied traditional reliability and validity criteria across multiple language datasets, supporting it as a clinically useful patient-reported instrument of satisfaction with anticoagulant treatment in clinical trials. NCT00440193

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Luke Bamber

Papers

Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study.

Epidemiology of first and recurrent venous thromboembolism: A population-based cohort study in patients without active cancer

Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism.

Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis

The Anti-Clot Treatment Scale (ACTS) in clinical trials: cross-cultural validation in venous thromboembolism patients