Consistency of safety and efficacy of new oral anticoagulants across subgroups of patients with atrial fibrillation.

AIMS: The well-known limitations of vitamin K antagonists (VKA) led to development of new oral anticoagulants (NOAC) in non-valvular atrial fibrillation (NVAF). The aim of this meta-analysis was to determine the consistency of treatment effects of NOAC irrespective of age, comorbidities, or prior VKA exposure. METHODS AND RESULTS: All randomized, controlled phase III trials comparing NOAC to VKA up to October 2012 were eligible provided their results (stroke/systemic embolism (SSE) and major bleeding (MB)) were reported according to age (≤ or >75 years), renal function, CHADS2 score, presence of diabetes mellitus or heart failure, prior VKA use or previous cerebrovascular events. Interactions were considered significant at p <0.05. Three studies (50,578 patients) were included, respectively evaluating apixaban, rivaroxaban, and dabigatran versus warfarin. A trend towards interaction with heart failure (p = 0.08) was observed with respect to SSE reduction, this being greater in patients not presenting heart failure (RR = 0.76 [0.67-0.86]) than in those with heart failure (RR = 0.90 [0.78-1.04]); Significant interaction (p = 0.01) with CHADS2 score was observed, NOAC achieving a greater reduction in bleeding risk in patients with a score of 0-1 (RR 0.67 CI 0.57-0.79) than in those with a score ≥2 (RR 0.85 CI 0.74-0.98). Comparison of MB in patients with (RR 0.97 CI 0.79-1.18) and without (RR 0.76 CI 0.65-0.88) diabetes mellitus showed a similar trend (p = 0.06). No other interactions were found. All subgroups derived benefit from NOA in terms of SSE or MB reduction. CONCLUSIONS: NOAC appeared to be more effective and safer than VKA in reducing SSE or MB irrespective of patient comorbidities. Thromboembolism risk, evaluated by CHADS2 score and, to a lesser extent, diabetes mellitus modified the treatment effects of NOAC without complete loss of benefit with respect to MB reduction

Deep vein thrombosis in Europe—health-related quality of life and mortality

Objectives: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT. Methods: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL—as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)—was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression. Results: At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%). Conclusions: Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT

Health-related quality of life and mortality in patients with pulmonary embolism: a prospective cohort study in seven European countries

PURPOSE: Little is known about the quality of life following pulmonary embolism (PE). The aim of the study was to assess the 12-month illness burden in terms of health-related quality of life (HrQoL) and mortality, in relation to differences in patient characteristics. METHODS: The PREFER in VTE registry, a prospective, observational study conducted in seven European countries, was used. Within 2 weeks following an acute symptomatic PE, patients were recruited and followed up for 12 months. Associations between patient characteristics and HrQoL (EQ-5D-5L) and mortality were examined using a regression approach. RESULTS: Among 1399 PE patients, the EQ-5D-5L index score at baseline was 0.712 (SD 0.265), which among survivors gradually improved to 0.835 (0.212) at 12 months. For those patients with and without active cancer, the average index score at baseline was 0.658 (0.275) and 0.717 (0.264), respectively. Age and previous stroke were significant factors for predicting index scores in those with/without active cancer. Bleeding events but not recurrences had a noticeable impact on the HrQoL of patients without active cancer. The 12-month mortality rate post-acute period was 8.1%, ranging from 1.4% in Germany, Switzerland, and Austria to 16.8% in Italy. Mortality differed between patients with active cancer and those without (42.7% vs. 4.7%). CONCLUSION: PE is associated with a substantial decrease in HrQoL at baseline which normalizes following treatment. PE is associated with a high mortality rate especially in patients with cancer, with significant country variation. Bleeding events, in particular, impact the burden of PE

Determination of rivaroxaban by different factor Xa specific chromogenic substrate assays: reduction of interassay variability

Rivaroxaban and other oral direct factor Xa inhibitors (ODiXa) are currently developed for prophylaxis and treatment of thromboembolic diseases using fixed doses. Although routine monitoring is not required, assessing the intensity of anticoagulation may be useful under certain clinical conditions. ODiXa prolong coagulation times of several clotting assays and, thus, their concentration may be determined in factor Xa specific chromogenic substrate assays. So far, no standardized and validated assay is commercially available. Here, five methods (A through E) are studied and optimized to reduce interassay variability. Human pooled plasma was spiked by a serial dilution of rivaroxaban (25–900 ng/ml). The release of para-nitroaniline from the chromogenic substrates was measured by the optical density (OD) at 405 nm. Method B was identified to yield the lowest sum of deviations from the mean value of the OD concentration curve calculated from all assays. Spline functions were developed for OD versus concentration curves for all methods. The calculated OD versus concentration curves overlapped for all methods. The coefficient of variation for all assays and concentrations of rivaroxaban decreased from 25.3 ± 11.4% using the original data to 3.8 ± 2.2% using the calculated data (P < 0.0001). The robustness of the chromogenic assay (method B) remains to be corroborated in interlaboratory comparisons

Primary thromboprophylaxis for cancer patients with central venous catheters – a reappraisal of the evidence

Venous thromboembolism (VTE) is responsible for an estimated 25 000 deaths per annum in UK hospital practice. It is well established that many of these deaths could be prevented through the use of appropriate thromboprophylaxis. This issue is of particular relevance in oncology practice, where the risks of VTE and bleeding are both significantly higher than those observed in general medical patients. Cancer patients with in-dwelling central venous catheters (CVCs) are at particularly high risk of developing thrombotic complications. However, the literature has produced conflicting conclusions regarding the efficacy of using routine primary thromboprophylaxis in these patients. Indeed such is the level of confusion around this topic, that the most recent version of the American College of Chest Physicians (ACCP) guidelines published in 2004 actually reversed their previous recommendation (published in 2001). Nevertheless, minidose warfarin continues to be routinely used in many oncology centres in the UK. In this article, we have performed a systematic review of the published literature regarding the efficacy and the risks, associated with using thromboprophylaxis (either minidose warfarin or low-dose LMWH) in cancer patients with CVC. On the basis of this evidence, we conclude that there is no proven role for using such thromboprophylaxis. However, asymptomatic CVC-related venous thrombosis remains common, and further more highly powered studies of better design are needed in order to define whether specific subgroups of cancer patients might benefit from receiving thromboprophylaxis

The potential benefits of low-molecular-weight heparins in cancer patients

Cancer patients are at increased risk of venous thromboembolism due to a range of factors directly related to their disease and its treatment. Given the high incidence of post-surgical venous thromboembolism in cancer patients and the poor outcomes associated with its development, thromboprophylaxis is warranted. A number of evidence-based guidelines delineate anticoagulation regimens for venous thromboembolism treatment, primary and secondary prophylaxis, and long-term anticoagulation in cancer patients. However, many give equal weight to several different drugs and do not make specific recommendations regarding duration of therapy. In terms of their efficacy and safety profiles, practicality of use, and cost-effectiveness the low-molecular-weight heparins are at least comparable to, and offer several advantages over, other available antithrombotics in cancer patients. In addition, data are emerging that the antithrombotics, and particularly low-molecular-weight heparins, may exert an antitumor effect which could contribute to improved survival in cancer patients when given for long-term prophylaxis. Such findings reinforce the importance of thromboprophylaxis with low-molecular-weight heparin in cancer patients

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes