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The novel direct oral anticoagulants (DOAC) have been shown to be at least as effective as and safer than conventional anticoagulants for the initial and long-term treatment of venous thromboembolic disorders. However, the rate of post-thrombotic syndrome (PTS) in patients with deep-vein thrombosis (DVT) treated with the DOACs is unknown. With the adoption of the Villalta scale, we assessed the rate of PTS at the end of the follow-up period in a consecutive series of 309 outpatients with acute proximal DVT who had received at least 3 months of treatment with a DOAC and had been followed-up for up to 3 years. The rate of PTS development was compared with that recorded in a historical cohort of 1036 consecutive patients who had been treated with vitamin K antagonists (VKA) and had received a similar follow-up examination. Logistic regression analysis, including propensity scoring to adjust for differing probabilities of undergoing VKA/DOAC, was used to identify predictors of PTS. PTS developed in 87 patients (28.2%) treated with the DOACs (severe in 12), and in 443 patients (42.8%) treated with VKAs (severe in 61). After adjusting for estimated propensity score, age, gender, concomitant symptoms of pulmonary embolism, duration of anticoagulation and development of residual vein thrombosis, the risk of PTS in the DOAC-treated patients was reduced by 54% in comparison to patients treated with conventional anticoagulation (odds ratio 0.46; 95% CI 0.33 to 0.63). We conclude that in comparison to VKAs, the use of the direct oral anticoagulants has the potential to offer a more favorable prognosis in terms of PTS development.

Despite the availability of updated guidelines for the diagnosis and treatment of venous thromboembolism (VTE), the management of this disorder in clinical practice is often not standardized, given the different degree of compliance with official recommendations by the various involved specialists. The aim of this consensus paper, as a result of a board of experts in thromboembolism, is to define strategies to improve the quality of patients' care and the efficiency of healthcare resources utilization, by means of: (a) analysis of the guidelines for diagnosis and treatment of VTE; (b) analysis of diagnostic and therapeutic algorithms currently used in clinical practice by different specialists; (c) agreement on a common algorithm for diagnosis and treatment of VTE in different clinical settings; (d) definition of the possible role of the new oral anticoagulant agents (NOAC), such as rivaroxaban, based on their potential benefits for both acute and chronic therapy. The so-called "single drug approach" (as opposed to the traditional heparin/VKA combination), which can be adopted with these drugs, makes anticoagulation more convenient for both patients and healthcare providers, without the need for a close monitoring of the hemocoagulative status, and with a concomitant reduction of length of hospitalization and treatment costs. Among NOACs, in this paper we focused on rivaroxaban only because it was the unique available NOAC in Italy for the treatment of VTE at the time the manuscript was written. Concerning rivaroxaban, the results of two phase III, randomized and controlled trials confirm the non-inferiority of this drug compared to standard therapy (enoxaparin/warfarin) for the treatment of patients with pulmonary embolism (EINSTEIN PE Study) or deep vein thrombosis (EINSTEIN DVT Study) in terms of both efficacy and safety, supporting its use as an effective therapeutic option for these disorders.

In the Hokusai-VTE trial, 733 patients were treated with the reduced dose edoxaban regimen, which maintained efficacy and safety compared with the 60 mg dose, and was safer than warfarin. The prophylactic doses of apixaban and rivaroxaban reduced the risk of recurrent venous thromboembolism (VTE) in the extended treatment trials. Dabigatran 110 mg was approved by the European Medicine Agency for VTE treatment. Further data from registries and real-world studies will help to clarify whether patients, with other specific characteristics, can benefit from the reduced dose of direct oral anticoagulants.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Real-life data on the clinical presentation, risk factors, diagnosis, and treatment of VTE in Italy and Europe are required to optimize the management of this disease. The PREFER in VTE registry, a prospective non-interventional real-life study, was designed to assess clinical characteristics and management of patients with VTE, use of health care resources, and on-treatment patient quality of life. Eligible consecutive patients with objectively diagnosed VTE were enrolled in the registry and followed up for 12 months. Between January and December 2013, 816 Italian and 1027 patients from 6 European countries other than Italy (European patients) were enrolled in the registry, and followed up until December 2014. Italian patients were the oldest (mean age 65.7 years) among the European patients. The Italian patients with a history of cancer were 24.6 % of whom 63.2 % had an active cancer (18.2 and 57.0 %, respectively, in Europe). Parenteral heparin was given, as initial treatment, in 73.8 % of Italian patients (66.4 % in Europe); VKA in combination with other treatments in 45.8 % (34.7 % in Europe); and VKA as the only anticoagulant treatment in 24.4 % (17.2 % in Europe). Of the Italian patients, 43.2 and 90.6 % of patients were hospitalized for deep vein thrombosis and pulmonary embolism, respectively; 65.4 % were admitted to the hospital through the emergency department. Following a real world approach, PREFER in VTE shows that the Italian patients, among and compared to the European patients, are the oldest, have a history of cancer more commonly, receive an initial treatment with heparin more commonly, and are more commonly hospitalized, particularly if affected by PE.

Currently available anticoagulants have limitations for long-term treatment of venous thromboembolism (VTE). We have evaluated the efficacy and safety of direct oral anticoagulants (DOACs) for extended treatment of VTE. Four randomized controlled trials (RCTs) comparing DOACs (apixaban, rivaroxaban, and dabigatran) with placebo or warfarin for extended treatment of VTE were published. Primary efficacy outcome was recurrent VTE or VTE-related death, and primary safety outcome was major bleeding. DOACs significantly lower the risk of recurrent VTE or VTE-related death compared to placebo/warfarin, as well as all-cause mortality. Risk of major bleeding is not different with DOACs compared to placebo/warfarin. However, DOACs are associated with a significantly higher rate of the composite of major and clinically relevant bleeding compared to placebo. In conclusion, DOACs are effective and safe for the extended treatment of VTE, and may reduce the risk of all-cause mortality.

Most cardiopulmonary diseases share at least one symptom with pulmonary embolism (PE). The aim of this study was to identify the most common acute causes of dyspnea, chest pain, fainting or palpitations, which diagnostic procedures were performed and whether clinicians investigate them appropriately. An Italian multicenter collaboration gathered 17,497 Emergency Department (ED) records of patients admitted from January 2007 to June 2007 in six hospitals. A block random sampling procedure was applied to select 800 hospitalised patients. Results of the overall 17,497 patients were obtained by weighting sampled cases according to the probability of the randomisation block variables in the whole population. The case-mix of enrolled patients was assessed in terms of cardiopulmonary symptoms, and the prevalence of acute disorders. The actual performance of procedures was compared with a measure of their accuracy as expected in the most common clinical presentations. PE occurred in less than 4% of patients with cardiopulmonary symptoms. Acute heart failure, pneumonia and chronic obstructive pulmonary disease exacerbation were the most likely diagnoses in patients with dyspnea. Acute myocardial infarction was present in roughly 10% of patients with chest pain. Atrial fibrillation was the prevalent diagnosis in patients with palpitations. Echocardiography, computed tomographic pulmonary angiography, perfusion lung scan, D-dimer test and B-type natriuretic peptide were performed less than expected from their accuracy. Diagnostic strategies, starting from non-specific symptoms and coping with the eventuality of PE, are likely to benefit from an increased awareness of the examination's accuracy in discriminating among several competing hypotheses, rather than in testing the single PE suspicion.

Venous thromboembolism (VTE) is a common potentially life-threatening complication in acutely ill medical patients; over 70 % of the fatal episodes of pulmonary embolism during hospitalization occur in non-surgical patients. In the absence of thromboprophylaxis, the incidence of venographically detected deep vein thrombosis is about 15 % in medical patients. Several trials and meta-analyses have clearly demonstrated the prophylactic role of unfractionated heparin, low molecular weight heparin and fondaparinux. Although over the past few years the knowledge of epidemiology, clinical features and prophylaxis in medical patients has significantly improved, there remain a number of controversial areas that require further investigation. Newer VTE risk assessment models have been proposed to select high risk hospitalized medical patients, but they still require external validation; scarce data are available to stratify patients to identify their individual bleeding risk. The optimal duration of thromboprophylaxis in medical patients is still a matter of debate; currently, extended prophylaxis after discharge is not recommended, but it may be required for subgroup of patients with persistently high VTE risk and a negligible risk of bleeding. Based on the results of recent studies, the new oral anticoagulants appear to have a very limited role, if any. However, a better risk stratification of patients who have a persistently increased risk of VTE is warranted to improve the risk to benefit profile of any anticoagulant drug to be used in this setting.

The prevalence of major risk factors for VTE may differ according to age, gender and clinical presentation. We tested this hypothesis in a large Italian VTE population. MASTER is a multicenter registry aimed to prospectively collect information on a large cohort of patients with acute VTE. The presence of major risk factors was captured by an electronic data network in consecutive patients with objectively confirmed acute VTE. We enrolled 2,119 patients (49.8% men) of whom 424 (20%) <40 years, 529 (25%) between 41 and 60 years, 943 (44.5%) between 61 and 80 years, and 223 (10.5%) >80 years. The prevalence of known risk factors in the four age groups is 63.9, 52.6, 54.6, and 58.3%, respectively (p = 0.002). Immobilization and severe medical disorders are more commonly associated with VTE in patients >80 years, trauma is significantly more common in patients <40 years than in older patient groups. The prevalence of unprovoked events is the highest in patients 41-60 years, and lowest in patients less than 40 years. After logistic regression analysis, patients with pulmonary embolism are more likely to have known risk factors for VTE than patients with deep vein thrombosis at presentation (p = 0.0021), and women are less likely than men to have an unprovoked VTE (p < 0.0001). In conclusion, a substantial proportion of VTE events remain classified as unprovoked. Unprovoked events are more common in middle aged patients, in men, and in patients presenting with deep vein thrombosis.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality following major orthopaedic surgery. However, the incidence of VTE and the role of additional risk factors have not yet been well explored in Italian clinical practice. The objective of the study is to estimate the incidence of VTE in the 3 months following elective hip and knee replacement (HR, KR) in a large cohort of patients, and the association between some selected risk factors and the occurrence of VTE. A large cohort study based on the record linkage between automated archives of the National Health System was analysed. In particular, all the residents in the Lombardy Region (Italy) who underwent HR and KR between 2005 and 2008 were followed for 3 months after surgery. The odds ratio (OR) of VTE associated with selected known risk factors was estimated by multivariate logistic regression. Amongst the 69,770 patients included in the study, 2,393 experienced at least one VTE event during the follow-up; the overall risk of VTE after HR or KR was 3.4%. The adjusted odds of experiencing a VTE event was higher in male patients (OR 1.11; 95% confidence interval 1.01-1.21), aged 60 years or older (1.30; 1.00-1.68), undergoing KR (1.47; 1.35-1.61), with previous deep vein thrombosis (1.96; 1.20-3.19), pulmonary embolism (3.25; 1.84-5.75) or cancer (1.21; 1.00-1.46). In conclusion, the incidence of VTE after elective HR and KR in the Italian clinical practice is high. Our results suggest the need of optimising the management of thromboprophylaxis to further reduce postoperative VTE.

Enoxaparin is the most frequently used low-molecular weight heparin in the world, given in order to prevent venous thromboembolism (VTE) in patients undergoing major orthopaedic surgery (MOS). Fondaparinux is an effective and safe alternative. The aim of our study was to compare the cost-effectiveness of enoxaparin and fondaparinux in the extended thromboprophylaxis of patients undergoing MOS in Italy. A decision-tree model was developed: probabilities of symptomatic events were derived from the published trials; use of resources in Italy was evaluated by means of a questionnaire administered to a panel of experts. Only the direct costs of VTE (acute treatment of events and of complications) were considered. Cost units were derived from the current cost of drugs, and from the Italian National Healthcare tariffs in 2007. Incremental cost-effectiveness ratios were analysed at three time points: 30 days, 1 year and 5 years. The higher cost of fondaparinux was counterbalanced by reduced rates of early DVT, early PE and prophylaxis-related major bleeding. If compared with enoxaparin, after 30 days of extended prophylaxis, fondaparinux is associated with a savings of 48.83 per patient; at the end of the first year, the savings increased to 72.13, and after 5 years, the savings are 74.36. One-way sensitivity analysis shows that the results are robust to the variation in unit costs for VTE-related care, or in event rates for both treatments. In conclusion, our model shows that, when administered for extended prophylaxis of VTE following MOS, fondaparinux is more effective and cost saving than enoxaparin.

Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopedic surgery. Routine thromboprophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of VTE in major orthopedic surgery include low molecular weight heparins, vitamin K antagonists, and, more recently, the synthetic pentasaccharide fondaparinux. Although effective, all these drugs have several limitations and new oral antithrombotics offering predictable, effective and safe anticoagulation are strongly needed. This overview focuses on the most advanced oral direct inhibitors to factor Xa rivaroxaban, apixaban, LY517717 and YM150; specifically, the results of phase II and III studies and the designs of ongoing clinical trials in patients undergoing elective hip and knee replacement are reviewed.

The close correlation between venous thromboembolism (VTE) and cancer has been known for some time, and numerous reports in the literature have highlighted the epidemiological significance. Moreover, VTE has a substantial impact on morbidity and mortality in oncological patients. The prevention and treatment of VTE are important aspects of the clinical management of patients with cancer. The presence of a tumour is often associated with thrombotic complications that are more difficult to diagnose, and sometimes make the treatment of VTE less effective and more likely to cause haemorrhages.