Secondary Prevention Of Venous Thromboembolism Research Articles

XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis.

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism, poses a substantial clinical risk, and the incidence of these thrombotic-related diseases remains high. Anticoagulation aims to prevent thrombus extension and reduce the risk of recurrent events, particularly fatal pulmonary embolism. In EINSTEIN DVT, rivaroxaban was non-inferior to enoxaparin/vitamin K antagonists for the reduction of recurrent VTE, with a similar safety profile and a net clinical benefit. EINSTEIN EXT investigated patients receiving long-term treatment in whom there was no clear decision about continuing or stopping anticoagulation; rivaroxaban was superior to placebo in the reduction of recurrent VTE, showing an acceptable benefit–risk balance. Rivaroxaban has the potential to replace standard therapy, usually parenteral low molecular weight heparin overlapping with and followed by a vitamin K antagonist, for the treatment of acute symptomatic DVT and the secondary prevention of VTE. As the use of rivaroxaban for DVT treatment increases in clinical practice, a fundamental understanding of its clinical benefits in everyday patient care is essential. XALIA (XArelto for Long-term and Initial Anticoagulation in venous thromboembolism) is a multicentre, prospective, non-interventional, observational study investigating the effectiveness and safety of a single-drug approach with rivaroxaban compared with standard therapy in patients with DVT. The study cohort will include approximately 4800 patients (≥18 years old) with objectively confirmed acute DVT who will be treated for a period of ≥3 months. The primary outcomes will be the incidence of treatment-emergent adverse events (primarily major bleeding), symptomatic recurrent venous thromboembolic events and all-cause mortality. Secondary outcomes include: major cardiovascular events; patient-reported treatment satisfaction and adherence; healthcare resource utilization; reasons for drug switching or interruption of treatment; and adverse events. XALIA will follow an international cohort of patients in more than 20 European countries, and others including Israel and Canada. The first patient was enrolled in June 2012, with results expected in 2015. It is anticipated that XALIA will provide important information on the treatment of DVT in a heterogeneous, unselected patient population in a real-world setting and provide important supplementary information to that obtained from the EINSTEIN DVT phase III study.

The role of novel anticoagulants in the management of venous thromboembolic disease.

The introduction of oral direct coagulation factor inhibitors is dramatically changing the landscape of anticoagulation delivery in patients experiencing or at risk for a thrombotic event. These novel anticoagulants can be particularly attractive for health care providers, as they deliver therapeutic anticoagulation at a fixed dose, require no routine coagulation monitoring, and have few drug interactions and no food restrictions. Herein, we will review the role of these novel anticoagulants for acute venous thromboembolism treatment, primary and secondary venous thromboembolism prevention, and management during the periprocedural period.

New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients

Patients with cancer have a 6–7-fold higher risk of venous thromboembolism (VTE) as compared with non-cancer patients. Effective and safe anticoagulation for the prevention and treatment of VTE is the cornerstone of the management of patients with cancer, aiming to decrease morbidity and mortality and to improve quality of life. Unfractionated heparin, low molecular weight heparins, fondaparinux and vitamin K antagonists (VKAs) are used in the prevention and treatment of VTE in cancer patients. Heparins and fondaparinux are administered subcutaneously. VKAs are orally active, but they have a narrow therapeutic window, numerous food and drug interactions, and treatment requires regular laboratory monitoring and dose adjustment. These limitations among others have important negative impact on the quality of life of patients and decrease adherence to the treatment. New orally active anticoagulant (NOAC) agents are specific inhibitors of activated factor Xa (FXa) (rivaroxaban and apixaban) or thrombin (dabigatran). It is expected that NOACs will improve antithrombotic treatment. Cancer patients are a particular group that could benefit from treatment with NOACs. However, NOACs present some significant interactions with drugs frequently used in cancer patients, which might influence their pharmacokinetics, compromising their efficacy and safety. In the present review, we analyzed the available data from the subgroups of patients with active cancer who were included in Phase III clinical trials that assessed the efficacy and safety of NOACs in the prevention and treatment of VTE. The data from the Phase III trials in prophylaxis of VTE by rivaroxaban or apixaban highlight that these two agents, although belonging to the same pharmacological group (direct inhibitors of factor Xa), have substantially different profiles of efficacy and safety, especially in hospitalized acutely ill medical patients with active cancer. A limited number of patients with VTE and active cancer were included in the Phase III trials (EINSTEIN, AMPLIFY, and RE-COVER) which evaluated the efficacy and safety of NOACs in the acute phase and secondary prevention of VTE. Although, from a conceptual point of view, NOACs could be an attractive alternative for the treatment of VTE in cancer patients, the available data do not support this option. In addition, due to the elimination of the NOACs by the liver and renal pathway as well as because of their pharmacological interactions with drugs which are frequently used in cancer patients, an eventual use of these drugs in cancer patients should be extremely cautious and be restricted only to patients presenting with contraindications for low molecular weight heparins, fondaparinux, or VKAs. The analysis of the available data presented in this review reinforces the request for the design of new Phase III clinical trials for the assessment of the efficacy and safety of NOACs in specific populations of patients with cancer.

Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results.

The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0119-7) contains supplementary material, which is available to authorized users.

Importance of thrombophilia screening

Thrombophilia testing denotes a test battery for inherited or acquired features associated with a tendency for clot formation. Currently, it is being used in a frequency and to an extent which is not supported by evidence. In order to protect patients from unnecessary worry and stigmatization, but also for reasons of cost effectiveness, thrombophilia testing should be reduced to a very small number of medically justifiable indications which are outlined in this review.Those indications include the following: secondary prevention of venous thromboembolism in patients from a thrombophilic family, i.e., with two or more first degree relatives with venous thromboembolism (VTE), or patients with suspected antiphospholipid syndrome; women prior to oral contraception or planning to become pregnant if they had no prior VTE but have one or more first-degree relatives with VTE-provided they are willing to follow the consequences of positive test results; women with recurrent miscarriage. The inappropriate indications are discussed as well.The test panel for inherited thrombophilias includes deficiencies of antithrombin, protein C and protein S, factor V Leiden and prothrombin 20210 mutation. Patients with suspicion of antiphospholipid syndrome have to be tested for lupus anticoagulans, anti-cardiolipin antibodies, and anti-β2-glycoprotein I-antibodies. It is important to do the blood sampling at an appropriate point in time.

Aspirin for prophylaxis of venous thromboembolism

Cessation of vitamin K antagonists (VKA) after a primary incidence of spontaneous venous thromboembolism (VTE) has been associated with recurrent events in about one-fifth of patients. Although long-term continuation of VKA prophylaxis has been suggested as a means to prevent recurrent VTE, concerns remain over issues of high bleeding risk, patient non-compliance as well as dosage irregularities. Antiplatelet therapy has been proposed as a safer, cheaper and more convenient alternative for long-term prophylaxis after initial treatment with VKA following VTE. Here we compare two major randomized trials that were conducted back-to-back – the WARFASA trial and the ASPIRE trial – to determine the role of aspirin as a long-term treatment option to reduce the incidence of recurrent VTE. Despite the encouraging results of these trials, suggesting that aspirin may have a beneficial effect on secondary prevention of VTE, it must be emphasized that both trials only started aspirin after 6-18 months of treatment with VKA, which remain a cornerstone of management for a first unprovoked VTE.

Use of aspirin for the prevention of lower extremity deep venous thrombosis.

Whereas aspirin is recommended and widely used to prevent arterial thrombosis, its role in the prevention of deep venous thrombosis is not well defined. Aspirin is well accepted, easy to manage with few risks and low cost, and thus ideal for thromboprophylaxis if evidence shows it is effective. Recent guidelines and large studies were reviewed. Recent guidelines include aspirin as an acceptable thromboprophylactic agent after hip and knee orthopedic surgery despite continued publication of underpowered and contradictory studies. Two large randomized controlled trials pooled together suggest that low-dose (100mg) aspirin is a reasonable alternative to prevent recurrence of venous thromboembolism (VTE) in patients who have been treated for a first episode of unprovoked VTE. We suggest that the current practice using aspirin to prevent thromboembolism include cautious discussion of the benefits and risks of this agent before use in a patient until precise clarification of dosage and treatment length is available. Despite inclusion of aspirin in the guidelines for orthopedic surgery, there is little evidence to support its use for primary prevention of VTE. Until definitive unbiased trials are published, we suggest that aspirin remain a realistic option to use for secondary prevention of VTE, especially compared with the option of using no prophylaxis.

Major bleeding during secondary prevention of venous thromboembolism in patients who have completed anticoagulation: a systematic review and meta‐analysis

SummaryBackgroundThe risk of major bleeding in patients who have completed anticoagulation therapy for unprovoked venous thromboembolism (VTE) is unknown.ObjectiveTo report the major bleeding and fatal bleeding rates in patients randomized to placebo or observation (i.e. no anticoagulation therapy) for the secondary prevention of recurrent VTE.Patients and methodsWe performed a systematic review and meta-analysis of the literature to summarize the rates of major bleeding and fatal bleeding in patients randomized to placebo or observation during the secondary prevention of VTE. Unrestricted searches of MEDLINE (January 1, 1950 to August 31, 2013), Embase (January 1, 1980 to August 31, 2013), and the Cochrane Register of Controlled Trials using the OVID interface were conducted. Publications from potentially relevant journals were also searched by hand. We used a random-effects model to pool study results and I2 testing to assess for heterogeneity.ResultsThe analysis included 11 studies and 3965 patients who were followed for a median of 24 months. The overall pooled major bleeding rate was 0.45 per 100 patient-years (95% CI 0.29–0.64, I2 = 0%), and the overall pooled fatal bleeding rate was 0.14 per 100 patient-years (95% CI 0.057–0.26, I2 = 0%).ConclusionsPatients not receiving anticoagulant therapy for the secondary prevention of VTE experience major bleeding events, and this may have an impact on recommendations for extended treatment in this patient population.

Pharmacokinetic and pharmacodynamic evaluation of rivaroxaban: considerations for the treatment of venous thromboembolism.

Patients with deep vein thrombosis or pulmonary embolism are recommended to receive anticoagulation for acute treatment and secondary prevention of venous thromboembolism (VTE). Fast-acting direct oral anticoagulants, with or without parenteral heparin, have the potential to replace vitamin K antagonists in this setting. Rivaroxaban, a direct Factor Xa inhibitor, is approved in the European Union and the United States for the single-drug treatment of deep vein thrombosis and pulmonary embolism and the secondary prevention of recurrent VTE in adults. The approved rivaroxaban dose schedule (15 mg twice daily for 3 weeks followed by 20 mg once daily) was derived based on pharmacological data from the clinical development programme to achieve a strong antithrombotic effect in the acute treatment phase and address the need to balance efficacy and bleeding risk for long-term treatment with a once-daily dose in the maintenance phase. Data from dose-ranging studies, pharmacokinetic modelling and randomised phase III trials support the use of this regimen. Other direct oral anticoagulants have also shown favourable efficacy and safety compared with standard treatment, and apixaban (European Union) and dabigatran (European Union and United States) have been approved in this indication. There are practical aspects to rivaroxaban use that must be considered, such as treatment of patients with renal and hepatic impairment, drug–drug interactions, monitoring of effect and management of bleeding. This review discusses the derivation of the VTE treatment regimen for rivaroxaban, summarises the clinical data for rivaroxaban and other direct oral anticoagulants in VTE treatment, and considers the practical aspects of rivaroxaban use in this setting.

Increased risk of myocardial infarction with dabigatran

Dabigatran is a direct, competitive inhibitor of thrombin recently approved for the prophylaxis of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In some of the clinical trials evaluating the efficacy and safety of dabigatran in different clinical settings [i.e., prevention of venous thromboembolism (VTE) after orthopedic surgery, secondary prevention of VTE, and acute coronary syndromes (ACS)], a trend toward an increase in acute coronary events among patients receiving dabigatran has been reported, thus raising concerns of a possible relationship between dabigatran and myocardial infarction, especially in high-risk patients. However, as shown in our article, current evidence is inconclusive on this topic; more data are needed to detail this hypothetical association, and other considerations, such as the well-known protective effect of warfarin against ACS, should be taken into account as a possible explanation.

Reversal of edoxaban-induced anticoagulation by the four-factor prothrombin complex concentrate Beriplex® in a rabbit model

The oral direct and selective factor Xa inhibitor edoxaban (Daiichi Sankyo) is currently available in Japan for the prophylaxis of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery and is undergoing investigation in phase III trials for the prevention of stroke in patients with atrial fibrillation and the treatment and secondary prevention of VTE. The primary complication of any available anticoagulant therapy is the risk of bleeding. Rapid reversal of anticoagulation may be necessary in patients requiring emergency treatment due to uncontrolled bleeding. Prothrombin complex concentrates (PCC) are frequently used to reverse the effect of vitamin K antagonists such as warfarin and have also been suggested to be potentially effective in reversing the effects of the new oral anticoagulants. The present study was therefore designed to determine whether the four-factor PCC Beriplex® can effectively reverse bleeding and normalize coagulation following edoxaban administration in a rabbit kidney injury model.

Pros and cons of new oral anticoagulants

The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time. Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients.

A clinical and pharmacologic assessment of once-daily versus twice-daily dosing for rivaroxaban

Altering doses and regimens of a drug has consequences for the drug's pharmacokinetic and pharmacodynamic profile. Based on a half-life of 5-13h, it is expected that the FactorXa inhibitor rivaroxaban would be best suited to a twice-daily rather than a once-daily dose regimen. However, although rivaroxaban is used as a twice-daily regimen for the initial treatment of venous thromboembolism (VTE) and secondary prevention after acute coronary syndromes, the approved dosing is once-daily for prevention of VTE after orthopaedic surgery, long-term secondary prevention of VTE and stroke prevention in patients with non-valvular atrial fibrillation. Rivaroxaban dosing was based on the evaluation of the efficacy and safety of several rivaroxaban doses and regimens in phase II trials. A clear overall advantage of twice-daily dosing compared with once-daily dosing was not documented for indications for which once-daily dosing was subsequently selected. Once-daily dosing was therefore selected for these indications because it is expected to be associated with better compliance than twice-daily dosing, and potentially, with improved outcomes. These studies and data obtained with another Factor Xa inhibitor, edoxaban, in addition to previous experience with low molecular weight heparins, indicate that the clinical impact of once-daily versus twice-daily doses on outcome in terms of efficacy and safety cannot be reliably predicted from pharmacology data, e.g. elimination half-life, obtained during pre-clinical and early phase I clinical studies but rather should be ascertained empirically in phase II and III clinical trials.

Renaissance of Aspirin for the Primary and Secondary Prevention of Venous Thromboembolism

Long-standing controversy has surrounded aspirin as an antithrombotic modality to prevent venous thromboembolism (VTE), particularly in the orthopedic surgery arena. New data are emerging on the use of aspirin for both primary VTE prevention and secondary prevention of recurrent VTE after an initial anticoagulation course. This review article will provide the history behind the controversy, information regarding recent or ongoing clinical trials of aspirin for primary VTE prevention in major orthopedic surgery, evidence for aspirin in secondary prevention of recurrent VTE, and suggestions for future research. Aspirin may be a reasonable option for VTE prevention in certain major orthopedic surgery patients. Additionally, investigation among non-orthopedic populations such as the acutely ill medical patient and the non-orthopedic surgery patient is encouraged to provide further safety and efficacy data.

Current and Former Smoking and Risk for Venous Thromboembolism: A Systematic Review and Meta-Analysis

Smoking is a well-established risk factor for atherosclerotic disease, but its role as an independent risk factor for venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis to summarize all published prospective studies and case-control studies to update the risk for VTE in smokers and determine whether a dose-response relationship exists. We performed a literature search using MEDLINE (source PubMed, January 1, 1966 to June 15, 2013) and EMBASE (January 1, 1980 to June 15, 2013) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-two observational studies involving 3,966,184 participants and 35,151 VTE events were identified. Compared with never smokers, the overall combined relative risks (RRs) for developing VTE were 1.17 (95% CI 1.09-1.25) for ever smokers, 1.23 (95% CI 1.14-1.33) for current smokers, and 1.10 (95% CI 1.03-1.17) for former smokers, respectively. The risk increased by 10.2% (95% CI 8.6%-11.8%) for every additional ten cigarettes per day smoked or by 6.1% (95% CI 3.8%-8.5%) for every additional ten pack-years. Analysis of 13 studies adjusted for body mass index (BMI) yielded a relatively higher RR (1.30; 95% CI 1.24-1.37) for current smokers. The population attributable fractions of VTE were 8.7% (95% CI 4.8%-12.3%) for ever smoking, 5.8% (95% CI 3.6%-8.2%) for current smoking, and 2.7% (95% CI 0.8%-4.5%) for former smoking. Smoking was associated with an absolute risk increase of 24.3 (95% CI 15.4-26.7) cases per 100,000 person-years. Cigarette smoking is associated with a slightly increased risk for VTE. BMI appears to be a confounding factor in the risk estimates. The relationship between VTE and smoking has clinical relevance with respect to individual screening, risk factor modification, and the primary and secondary prevention of VTE. Please see later in the article for the Editors' Summary.

Bioavailability and Safety of the Factor Xa Inhibitor Edoxaban and the Effects of Quinidine in Healthy Subjects.

Edoxaban is an oral, once-daily, direct factor Xa inhibitor under investigation for stroke prevention in patients with atrial fibrillation and for treatment and secondary prevention of venous thromboembolism. This study evaluated edoxaban absolute bioavailability and effects of the P-glycoprotein inhibitor quinidine on edoxaban pharmacokinetics after intravenous edoxaban administration. Healthy volunteers received three treatments in a randomized sequence: single oral 60-mg edoxaban dose, single intravenous 30-mg edoxaban dose, and concomitant single intravenous 30-mg edoxaban dose with quinidine 300 mg every 8 hours for 4 days. The primary objective was to determine absolute bioavailability of edoxaban. Secondary objectives included pharmacokinetics and pharmacodynamics of edoxaban after oral or intravenous administration, quinidine effect on intravenous edoxaban pharmacokinetics, and safety. Thirty-six subjects were randomized; five discontinued (three for adverse events [AEs]). Edoxaban oral absolute bioavailability was 61.8%. With concomitant quinidine, total edoxaban exposure increased ∼35% and total clearance decreased ∼25%. Coagulation parameters increased after edoxaban administration in most subjects, but returned to baseline within 24 hours postdose. No deaths, serious AEs, or bleeding-related AEs occurred. Absolute bioavailability of edoxaban in healthy volunteers was established (61.8%). Edoxaban, administered orally or intravenously, appeared to be safe and well tolerated.

Treatment with novel oral anticoagulants

To summarize data relevant to novel oral anticoagulants (nOACs), mainly apixaban, dabigatran and rivaroxaban, as alternatives to vitamin K antagonists (VKAs). RE-LY was the first contemporaneous study to compare a nOAC, dabigatran, with dose-adjusted warfarin, for prevention of stroke and systemic embolism in atrial fibrillation. Since then multiple studies have compared nOACs to warfarin for acute (RE-COVER, RECOVER-II, EINSTEIN-DVT and EINSTEIN-PE) and extended treatment of venous thromboembolism (VTE) (AMPLIFY-EXT, RE-MEDY and RE-SONATE). Additional studies have examined stroke prevention in atrial fibrillation (ARISTOTLE and ROCKET-AF). We do not examine, in depth, use of nOACs in coronary artery disease. nOACs are an acceptable alternative to VKAs in certain situations - these are at least as effective as warfarin for secondary prevention of VTE and for prevention of stroke and systemic embolism in patients with atrial fibrillation. These compare favorably with warfarin with respect to their rate of fatal and major bleeding. However, special attention should be given when using these drugs in certain patient populations, in particular in patients with renal insufficiency, those receiving additional antithrombotic therapy, those with questionable compliance, patients of child bearing potential and those with a high risk of gastrointestinal bleeding.

Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis

Objective To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of...

The predictive ability of bleeding risk stratification models in very old patients on vitamin K antagonist treatment for venous thromboembolism: results of the prospective collaborative EPICA study

The optimal duration of anticoagulant treatment after venous thromboembolism (VTE) should be evaluated in relation to bleeding risk. This assessment is particularly difficult with elderly patients, because of their increased risk of both recurrences and hemorrhages. Bleeding risk stratification models have been proposed, but their predictive ability in very elderly patients is unknown. We aimed to assess six bleeding stratification models in this setting, by using information available in our dataset. Patients aged ≥ 80 years receiving vitamin K antagonists (VKAs) for the secondary prevention of VTE were eligible for this prospective cohort study. All patients were followed at Italian anticoagulation clinics for monitoring of VKA treatment. Risk factors for bleeding were collected, and major bleeding events and mortality were documented during follow-up. The association of bleeding events with the available risk factors was tested by means of Cox regression analysis; the c-statistic was used to quantify the predictive validity of the classification schemes. A total of 1078 patients (37.2% males; mean age, 84 years) were enrolled in the study, for a total observation period of 1981 patient-years. The rate of major bleeding was 2.4 per 100 patient-years (47 events; one was fatal). The mortality rate was 5.2 per 100 patient-years. None of the considered risk factors were significantly associated with bleeding events. The predictive validity of the risk stratification models was low, and the most accurate model was not specifically developed for VTE patients (HEMORR2 HAGES, c-statistic 0.60, 95% confidence interval 0.49-0.70). Bleeding risk stratification models appear to have little accuracy in very elderly VTE patients.

Rivaroxaban for the Treatment of Pulmonary Embolism

With the advent of new oral anticoagulants (NOACs) for the treatment of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE), a new era of oral anticoagulation for patients with venous thromboembolism (VTE) has begun. Rivaroxaban is the first NOAC to receive regulatory approval for the acute and continued treatment of DVT and PE, and for the secondary prevention of VTE. Here, the clinical trials of rivaroxaban in patients with VTE are reviewed, and the clinical use of rivaroxaban for patients with PE is discussed. Even though rivaroxaban will facilitate the therapeutic management of PE, its use in specific clinical situations needs further study.