Background
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.
Methods
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.
Results
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.
Conclusions
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.
Summary
Background
Patients with cancer have an increased risk of venous thromboembolism (VTE) and it is commonly detected incidentally. The outcomes and optimal management for patients with cancer ...and incidental VTE remain debated.
Objectives
We conducted a systematic review and meta‐analysis to evaluate the outcomes in patients with cancer and incidentally detected VTE compared to those with symptomatic events.
Patients/Methods
We searched the electronic databases and included randomized controlled trials (RCTs) and observational studies reporting recurrent VTE, major bleeding events, and mortality in patients with cancer and incidental VTE compared to symptomatic VTE.
Results
We included 23 studies for the systematic review: 3 RCTs and 20 observational studies. The meta‐analysis of the 3 RCTs showed a significantly lower rate of VTE recurrence at 6 months in patients with incidental VTE compared to those with symptomatic VTE (relative risk RR 0.62, 95% confidence interval CI 0.44–0.87). The risk of major bleeding events at 6 months was numerically higher with incidental VTE compared to symptomatic VTE (RR 1.47, 95% CI 0.99–2.20). There was no difference in overall mortality.
Conclusions
Among patients with cancer, incidental VTE was associated with a lower rate of VTE recurrence compared to symptomatic VTE, with a trend in increased major bleeding events. The risk‐benefit ratio of anticoagulation may differ between incidental and symptomatic events and should be considered in patient management.
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 .).
Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending ...primary thromboprophylaxis, in those identified at high‐risk of VTE by the presence of risk factors. The National Comprehensive Cancer Network (NCCN) has adopted these guidelines; however, they lack validation. We sought to develop and validate a risk prediction score for VTE in MM and to evaluate the performance of the current IMWG/NCCN guidelines. Using 4446 patients within the Veterans Administration Central Cancer Registry, we used time‐to‐event analyses to develop a risk score for VTE in patients with newly diagnosed MM starting chemotherapy. We externally validated the score using the Surveillance, Epidemiology, End Results (SEER)‐Medicare database (N = 4256). After identifying independent predictors of VTE, we combined the variables to develop the IMPEDE VTE score (Immunomodulatory agent; Body Mass Index ≥25 kg/m2; Pelvic, hip or femur fracture; Erythropoietin stimulating agent; Dexamethasone/Doxorubicin; Asian Ethnicity/Race; VTE history; Tunneled line/central venous catheter; Existing thromboprophylaxis). The score showed satisfactory discrimination in the derivation cohort, c‐statistic = 0.66. Risk of VTE significantly increased as score increased (hazard ratio 1.20, P = <.0001). Within the external validation cohort, IMPEDE VTE had a c‐statistic of 0.64. For comparison, when evaluating the performance of the IMWG/NCCN guidelines, the c‐statistic was 0.55. In summary, the IMPEDE VTE score outperformed the current IMWG/NCCN guidelines and could be considered as the new standard risk stratification for VTE in MM.
Background
Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps ...in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE).
Methods
We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis.
Results
We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing.
Discussion
Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non‐haemophilic patients. Prospective data are needed to inform optimal and evidence‐based management strategies of CVD and VTE in persons with haemophilia.
Obesity has become a major threat to health worldwide. The prevalence of obesity is rapidly increasing, so much so that the World Health Organization has declared obesity as a global epidemic. ...Obesity is associated with multiple health problems, including venous thromboembolism and atrial fibrillation, both of which are treated with anticoagulation. However, obesity and treatments for obesity such as bariatric surgery can influence absorption, excretion, pharmacokinetics, and pharmacodynamics of various anticoagulants. This results in uncertainty regarding the best antithrombotic strategies in this population, particularly in the morbidly obese. In the recent years, several studies have attempted to investigate anticoagulation use in this population and provided more insight. Herein, we present 4 cases of anticoagulant use in the obese to illustrate the common challenges faced by clinicians and discuss our approach. Whenever possible, we provide a review of the literature and base our recommendations on the best available evidence.
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