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The anticoagulant edoxaban, an oral inhibitor of activated factor X, does not require monitoring. As initial treatment for acute venous thromboembolism, heparin–edoxaban was noninferior to heparin–warfarin and caused less bleeding. Venous thromboembolism is the third most common cardiovascular disease after myocardial infarction and stroke, affecting at least 700,000 persons annually in North America. 1 – 3 The standard treatment consists of low-molecular-weight heparin followed by vitamin K antagonists. 4 A number of studies have established that new oral anticoagulants with or without initial heparin therapy are effective alternatives. 5 – 8 Edoxaban is a direct inhibitor of activated factor X with a rapid onset of action. It is administered orally once daily and has proven antithrombotic efficacy. 9 – 11 The Hokusai-VTE study was a randomized, double-blind clinical trial that was conducted to evaluate edoxaban for the . . .

Background and Objective: Rivaroxaban is an oral, direct Factor Xa inhibitor, which is at an advanced stage of clinical development for prevention and treatment of thromboembolic disorders. Two phase II studies, ODIXa-DVT and EINSTEIN DVT, assessed the efficacy and safety of oral rivaroxaban (once daily or twice daily) for treatment of acute deep-vein thrombosis (DVT). Population pharmacokinetic and pharmacodynamic analyses of rivaroxaban in patients in these two phase II studies were conducted to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban and the relationship between important patient covariates and model parameters. Exposure simulations in patients with atrial fibrillation (AF) were also performed in order to predict the exposure of rivaroxaban, using modified demographic data reflecting the characteristics of a typical AF population. Methods: A population pharmacokinetic model was developed using plasma samples from these patients. Various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with AF. Correlations between plasma rivaroxaban concentrations and the prothrombin time, Factor Xa activity, HepTest® and activated partial thromboplastin time were also described. Results: The pharmacokinetics of rivaroxaban in patients with DVT were found to be consistent and predictable across all doses studied. The area under the plasma concentration-time curve (AUC) increased dose dependently. The same total daily doses given once daily achieved higher maximum plasma concentration (C max ) values (∼20%) and lower trough (minimum) plasma concentration (C trough ) values (∼60%) than when given twice daily; however, the 5th–95th percentile ranges for these parameters overlapped. Rivaroxaban clearance was moderately influenced by age and renal function, and the volume of distribution was influenced by age, body weight and sex; the effects were within the observed interindividual variability. Simulations in virtual patient populations with AF showed that a rivaroxaban dose of 15 mg once daily in patients with creatinine clearance of 30–49 mL/min would achieve AUC and C max values similar to those observed with 20 mg once daily in patients with normal renal function. The prothrombin time correlated almost linearly with plasma rivaroxaban concentrations (≤500 µg/L). Conclusion: Population analyses of phase II clinical data indicated that the pharmacokinetics and pharmacodynamics of all rivaroxaban doses were predictable and were affected by expected demographic factors in patients with acute DVT.

Superficial thrombophlebitis in the leg is associated with an increased risk of subsequent thromboembolic events; however, intervention to alter the risk has not been well studied. This study compared fondaparinux with placebo for patients with superficial thrombophlebitis in the leg. Superficial-vein thrombosis of the legs is a common condition, 1 , 2 with an estimated incidence that may exceed that of deep-vein thrombosis. 3 , 4 Patients with isolated superficial-vein thrombosis — that is, without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation — are at risk for subsequent symptomatic venous thromboembolic complications. 1 – 7 In a large, prospective, observational study, the 3-month risk of such complications was 8.3%, with a 3.3% risk of deep-vein thrombosis or pulmonary embolism. 8 The treatment of this disease has not been adequately addressed in randomized trials. Accordingly, the recommendations in various guidelines are weak, and in practice, therapeutic . . .

Background Venous thromboembolism (VTE, including deep vein thrombosis [DVT] and pulmonary embolism [PE]) has an annual incidence rate of 104–183 per 100,000 person-years. After a VTE episode, the two-year recurrence rate is about 17%. Consequently, effective and safe anticoagulation is paramount. Edoxaban is a direct oral anticoagulant (DOAC) approved VTE treatment. Current safety and efficacy data are derived from clinical trials, and information about treatment durations beyond 12 months are not available. Methods ETNA-VTE-Europe is an 18-month prospective, single-arm, non-interventional, multinational post-authorisation safety study. Approximately 310 sites across eight European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Switzerland and the United Kingdom) will participate in the study, with the intention to represent the regional distributions of centres, healthcare settings and specialties. An estimated cohort of 2700 patients will be recruited, the only enrolment criteria being acute symptomatic VTE, no participation in an interventional study, and treating physician decision to prescribe edoxaban independently from the registry. Data from patient medical records and/or telephone interviews will be collected at baseline, 1, 3, 6, 12 and 18 months. The primary objective is to evaluate the 18-month rate of symptomatic VTE recurrence in patients with VTE treated with edoxaban outside a clinical trial. The co-primary objective is to evaluate the real-world rates of bleeding and adverse drug reactions. Secondary outcomes include rates of other patient-relevant safety events, adherence to and discontinuation of edoxaban. Furthermore, 12-month ETNA-VTE-Europe data will be considered in the context of those for patients receiving different anticoagulants in the PREFER in VTE registry and Hokusai-VTE clinical trial. Conclusions ETNA-VTE-Europe will allow the safety and effectiveness of edoxaban to be evaluated over an extended period in acute symptomatic VTE patients encountered in routine clinical practice. Findings will be informative for European practitioners prescribing edoxaban as part of real-world VTE treatment/prevention. Trial registration ClinicalTrials.gov Identifier: NCT02943993 .

Background Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. Methods A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. Results A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66–1.19; p noninferiority  < 0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37–0.79; p = 0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots, and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban were similar compared with standard-therapy. Conclusion The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups. Trial registration EINSTEIN-PE: ClinicalTrials.gov, NCT00439777 ; EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193 .

In the treatment of patients with acute pulmonary embolism, the efficacy of rivaroxaban, a factor Xa inhibitor, was similar to that of traditional anticoagulation therapy. There was less bleeding in the group receiving rivaroxaban, which supports its use in the treatment of this condition. Pulmonary embolism is a common disease, with an estimated annual incidence of 70 cases per 100,000 population. 1 , 2 The condition usually leads to hospitalization and may recur; it can be fatal. 3 For half a century, the standard therapy for most patients with pulmonary embolism has been the administration of heparin, overlapped and followed by a vitamin K antagonist. 4 , 5 This regimen is effective but complex. 5 – 9 Recently developed oral anticoagulants that are directed against factor Xa or thrombin overcome some limitations of standard therapy, including the need for injection and for regular dose adjustments on the basis of laboratory monitoring. . . .

In this clinical trial, rivaroxaban, an oral factor Xa inhibitor, was effective in the initial and continued treatment of symptomatic venous thromboembolism; it may become part of the treatment armamentarium for this common clinical problem. Acute venous thromboembolism (i.e., deep-vein thrombosis [DVT] or pulmonary embolism) is a common disorder with an annual incidence of approximately 1 or 2 cases per 1000 persons in the general population. 1 , 2 Short-term treatment is effective, with the risk of recurrent disease — the major complication — reduced from an estimated 25% to about 3% during the first 6 to 12 months of therapy. 3 The risk of recurrence remains after treatment ends and can reach 5 to 10% during the first year. 4 , 5 Standard treatment for acute venous thromboembolism is limited by the need for parenteral heparin initially, with overlapping . . .

[This corrects the article DOI: 10.1186/s12959-018-0163-7.].

The long-acting factor X inhibitor idraparinux was compared with a standard antithrombotic regimen in two randomized trials, one for the treatment of deep venous thrombosis (DVT Study) and the other for the treatment of pulmonary embolism (PE Study). In the DVT Study, idraparinux was not inferior to standard therapy. In the PE Study, idraparinux was less efficacious than standard therapy. For the treatment of deep venous thrombosis, idraparinux was not inferior to standard therapy. For the treatment of pulmonary embolism, idraparinux was less efficacious than standard therapy. The standard treatment for both deep venous thrombosis and pulmonary embolism is an initial course of unfractionated heparin or low-molecular-weight heparin, followed by a vitamin K antagonist for 3 to 12 months. 1 , 2 This therapy is effective but requires laboratory monitoring and dose adjustments. Idraparinux (Sanofi-Aventis) is a novel synthetic pentasaccharide that inhibits activated factor X and differs from fondaparinux in its substantially longer half-life. Initial clinical experience suggests that a fixed dose given subcutaneously once weekly is effective and causes less bleeding than vitamin K antagonists in the treatment of venous thromboembolism. 3 , 4 In two studies in patients presenting . . .

The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin). To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis. Randomized, double-blind study. 154 centers worldwide. 2205 patients with acute symptomatic deep venous thrombosis. Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes. 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively. Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients. Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.