rivaroxaban and Pulmonary-Embolism

Topics: Anticoagulants; Child; Humans; Nephrotic Syndrome; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

To summarize the incidence, risk factors, diagnosis methods, prophylaxis methods, and treatment of venous thromboembolism (VTE) following arthroscopic shoulder surgery.. Literature on VTE after arthroscopic shoulder surgeries was summarized, and all primary full-text articles reporting at least 1 case of deep vein thrombosis (DVT) or pulmonary embolism (PE) after arthroscopic shoulder surgeries were included. Articles were critically appraised and systematically analyzed to determine the incidence, risk factors, diagnosis, prophylaxis, and management of VTE following arthroscopic shoulder surgeries.. Based on the included studies, the incidence rate of VTE after arthroscopic shoulder surgeries is relatively low. The risk factors for VTE are still unclear. CT/CTA and ultrasound were the mainstream diagnosis methods for PE and DVT, respectively. Current evidence shows that chemical prophylaxis did not deliver significant benefits, since none of the existing studies reported statistically different results. High-quality studies focusing on the prophylaxis and management of VTE population undergoing arthroscopic shoulder surgeries should be done in the future.

Topics: Aged; Anticoagulants; Humans; Incidence; Pulmonary Embolism; Risk Factors; Rivaroxaban; Shoulder; Venous Thromboembolism; Warfarin

Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT.. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022.. We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome.. We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortal

Topics: Anticoagulants; Antithrombins; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasm Recurrence, Local; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

This review summarizes current evidence and guideline recommendations concerning diagnosis and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). For the diagnostic pathway, evidence-based algorithms should be employed, based on the assessment of pretest clinical probability. D‑dimer tests may reduce the need for subsequent diagnostic procedures. Clinical management of PE is guided by risk stratification according to early mortality. Lactate levels may be helpful for further risk stratification. The acute treatment of venous thromboembolism (VTE) is commenced with intensified anticoagulation (AC), either with parenteral AC or higher initial doses of apixaban or rivaroxaban. All patients with VTE should receive the anticoagulation maintenance therapy for 3-6 months, while the duration of the subsequent secondary prophylaxis depends on the presumed risk of VTE recurrence and bleeding. Compression therapy is used to prevent postthrombotic syndrome. Acute revascularization procedures are limited to rare special cases. In obese patients up to 150 kg, standard doses of rivaroxaban and apixaban are appropriate. In cancer-associated thromboembolism (CAT), the previous guideline recommendation to use low molecular weight heparin (LMWH) for 3-6 months is now broadened with the recommendation for factor Xa inhibitors, with the caveat for gastrointestinal and urothelial cancer or expected drug-drug interactions with the anticancer treatment. Here, and in unstable clinical situations, LMWH is preferred.. In dieser Übersichtsarbeit werden die aktuelle Evidenz und Empfehlungen aus aktuellen Leitlinien zur Diagnostik und Therapie von tiefer Venenthrombose (TVT) und Lungenembolie (LE) zusammengefasst. Für den Diagnoseprozess soll ein evidenzbasierter Algorithmus verwendet werden, der mit der Abschätzung der klinischen Wahrscheinlichkeit beginnt. Unter Berücksichtigung des D‑Dimer-Tests kann die Notwendigkeit für die nachfolgende bildgebende Diagnostik reduziert werden. Bei der LE leitet die Stratifizierung entsprechend der Frühmortalität das weitere klinische Management. Die Messung von Laktat kann für diese Risikoeinschätzung hilfreich sein. Die Akuttherapie der venösen Thromboembolie (VTE) erfolgt intensiviert entweder mit parenteralen Antikoagulanzien oder erhöhten Dosierungen von Apixaban oder Rivaroxaban. Alle Patienten mit VTE sollten eine Erhaltungstherapie über 3–6 Monate erhalten, da bei einer Antikoagulation (AK) < 3 Monaten ein hohes Rezidivrisiko besteht. Die Dauer der anschließenden Sekundärprophylaxe richtet sich nach dem mutmaßlichen VTE-Rezidivrisiko einerseits und dem Blutungsrisiko andererseits. Weiterhin wird eine Kompressionstherapie zur Verhinderung des postthrombotischen Syndroms empfohlen, akut revaskularisierende Eingriffe sind Sonderfällen vorbehalten. Bei Adipositas bis 150 kg werden Standarddosen von Rivaroxaban und Apixaban als geeignet vorgeschlagen. Bei der krebsassoziierten Thromboembolie wird die bisherige Leitlinienempfehlung für niedermolekulare Heparine (NMH) über 3–6 Monate ergänzt durch die Empfehlung für Faktor-Xa-Inhibitoren, allerdings mit Vorsicht bei gastrointestinalen und urothelialen Tumoren oder erwarteten Wechselwirkungen mit der Antikrebstherapie. Hier und in instabilen Phasen werden NMH bevorzugt.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

A systematic review and meta-analysis was performed to determine the role of thromboprophylaxis in the prevention of venous thromboembolism in patients undergoing varicose vein interventions.. PUBMED, EMBASE and Web of Science were searched for comparative studies of patients undergoing varicose vein interventions and received either thromboprophylaxis or no thromboprophylaxis. Data were collected on the number of thrombotic events including deep vein thrombosis (DVT), pulmonary embolism (PE) and endothermal heat-induced thrombosis (EHIT) as well as bleeding events. The primary outcomes for the meta-analysis were the risk of all thrombotic events, risk of DVT and risk of bleeding. Pooled risk ratios were calculated using random effects modelling.. Eight studies (6479 participants) were included. The use of thromboprophylaxis reduces the risk of all thrombotic events (Pooled risk ratio = 0.63, 95% Confidence interval [CI], 0.04-10.43) and the risk of DVT (Pooled risk ratio = 0.59, 95% CI, 0.08-4.60) with no increased risk of bleeding (Pooled risk ratio = 0.66, 95% CI, 0.06-7.21]. Rivaroxaban has similar efficacy in the prevention of DVT compared to Fondaparinux in patients undergoing endovenous ablation of varicose veins (Pooled risk ratio = 0.68, 95% CI, 0.06-7.41). An extended course of thromboprophylaxis reduces the risk of developing DVT compared to a short course (Pooled risk ratio = 1.40, 95% CI, 0.44-4.46). However, the two studies reporting on the duration of thromboprophylaxis did not stratify patients according to their risk of developing venous thromboembolism.. The use of thromboprophylaxis in patients undergoing varicose vein interventions reduces the risk of venous thromboembolism with no significant increase in the risk of bleeding. However, the included studies were underpowered with high to moderate risk of bias. Therefore, more randomised controlled trials with a large sample size are needed in order to provide high quality evidence for clinical practice.

Topics: Humans; Pulmonary Embolism; Rivaroxaban; Varicose Veins; Venous Thromboembolism

Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and, in suitable cases, to assist the diagnosis of persistent knee pain. There is a small risk of thromboembolic events associated with KA. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This is an update of an earlier Cochrane Review.. To evaluate the efficacy and safety of interventions - whether mechanical, pharmacological, or a combination of both - for thromboprophylaxis in adults undergoing KA.. We used standard, extensive Cochrane search methods. The latest search date was 1 June 2021.. We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), blinded or unblinded, of all types of interventions used to prevent deep vein thrombosis (DVT) in men and women aged 18 years and older undergoing KA.. We used standard Cochrane methods. Our primary outcomes were pulmonary embolism (PE), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Our secondary outcomes were adverse effects, major bleeding, and minor bleeding. We used GRADE criteria to assess the certainty of the evidence.. We did not identify any new studies for this update. This review includes eight studies involving 3818 adults with no history of thromboembolic disease. Five studies compared daily subcutaneous low-molecular-weight heparin (LMWH) versus no prophylaxis; one study compared oral rivaroxaban 10 mg versus placebo; one study compared daily subcutaneous LMWH versus graduated compression stockings; and one study compared aspirin versus no prophylaxis. The incidence of PE in all studies combined was low, with seven cases in 3818 participants. There were no deaths in any of the intervention or control groups. Low-molecular-weight heparin versus no prophylaxis When compared with no prophylaxis, LMWH probably results in little to no difference in the incidence of PE in people undergoing KA (risk ratio [RR] 1.81, 95% confidence interval [CI] 0.49 to 6.65; 3 studies, 1820 participants; moderate-certainty evidence). LMWH may make little or no difference to the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 4 studies, 1848 participants; low-certainty evidence). It is uncertain whether LMWH reduces the risk of asymptomatic DVT (RR 0.14, 95% CI 0.03 to 0.61; 2 studies, 369 participants; very low-certainty evidence). LMWH probably makes little or no difference to the risk of all adverse effects combined (RR 1.85, 95% CI 0.95 to 3.59; 5 studies, 1978 participants; moderate-certainty evidence), major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; moderate-certainty evidence), or minor bleeding (RR 1.79, 95% CI 0.84 to 3.84; 5 studies, 1978 participants; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. There were no cases of PE reported. Rivaroxaban probably led to little or no difference in symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence). It is uncertain whether rivaroxaban reduces the risk of asymptomatic DVT because the certainty of the evidence is very low (RR 0.95, 95% CI 0.06 to 15.01). The study only reported bleeding adverse effects. No major bleeds occurred in either group, and rivaroxaban probably made little or no difference to minor bleeding (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus no prophylaxis One study compared aspirin with no prophylaxis. There were no PE, DVT or asymptomatic events detected in either group. The study authors reported adverse effects including pain and swelling, but wit. There is a small risk that healthy adults undergoing KA will develop venous thromboembolism (PE or DVT). We found moderate- to low-certainty evidence of little or no benefit from LMWH, or rivaroxaban in reducing this small risk of PE or symptomatic DVT. The studies provided very low-certainty evidence that LMWH may reduce the risk of asymptomatic DVT compared to no prophylaxis, but it is uncertain how this directly relates to incidence of DVT or PE in healthy people undergoing KA. There is probably little or no difference in adverse effects (including major and minor bleeding), but data relating to these outcomes were limited by low numbers of events in the studies reporting these outcomes.

Topics: Adult; Anticoagulants; Arthroscopy; Aspirin; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Pain; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Pulmonary embolism (PE) is characterized by occlusion of blood flow in a pulmonary artery, typically due to a thrombus that travels from a vein in a lower limb. The incidence of PE is approximately 60 to 120 per 100 000 people per year. Approximately 60 000 to 100 000 patients die from PE each year in the US.. PE should be considered in patients presenting with acute chest pain, shortness of breath, or syncope. The diagnosis is determined by chest imaging. In patients with a systolic blood pressure of at least 90 mm Hg, the following 3 steps can be used to evaluate a patient with possible PE: assessment of the clinical probability of PE, D-dimer testing if indicated, and chest imaging if indicated. The clinical probability of PE can be assessed using a structured score or using clinical gestalt. In patients with a probability of PE that is less than 15%, the presence of 8 clinical characteristics (age <50 years, heart rate <100/min, an oxygen saturation level of > 94%, no recent surgery or trauma, no prior venous thromboembolism event, no hemoptysis, no unilateral leg swelling, and no estrogen use) identifies patients at very low risk of PE in whom no further testing is needed. In patients with low or intermediate clinical probability, a D-dimer level of less than 500 ng/mL is associated with a posttest probability of PE less than 1.85%. In these patients, PE can be excluded without chest imaging. A further refinement of D-dimer threshold is possible in patients aged 50 years and older, and in patients with a low likelihood of PE. Patients with a high probability of PE (ie, >40% probability) should undergo chest imaging, and D-dimer testing is not necessary. In patients with PE and a systolic blood pressure of 90 mm Hg or higher, compared with heparin combined with a vitamin K antagonist such as warfarin followed by warfarin alone, direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, are noninferior for treating PE and have a 0.6% lower rate of bleeding. In patients with PE and systolic blood pressure lower than 90 mm Hg, systemic thrombolysis is recommended and is associated with an 1.6% absolute reduction of mortality (from 3.9% to 2.3%).. In the US, PE affects approximately 370 000 patients per year and may cause approximately 60 000 to 100 000 deaths per year. First-line therapy consists of direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, with thrombolysis reserved for patients with systolic blood pressure lower than 90 mm Hg.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Dabigatran; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Pulmonary Embolism; Risk; Rivaroxaban; United States; Vitamin K; Warfarin

Venous thromboembolism (VTE) is the leading preventable cause of death in hospitalized patients and data consistently show that acutely ill medical patients remain at increased risk for VTE-related morbidity and mortality in the post-hospital discharge period. Prescribing extended thromboprophylaxis for up to 45 days following an acute hospitalization in key patient subgroups that include more than one-quarter of hospitalized medically-ill patients represents a paradigm shift in the way hospital-based physicians think about VTE prevention. Advances in the field of primary thromboprophylaxis in acutely-ill medical patients using validated VTE and bleeding risk assessment models have established key patient subgroups at high risk of VTE and low risk of bleeding that may benefit from both in-hospital and extended thromboprophylaxis. The direct oral anticoagulants betrixaban and rivaroxaban are now U.S. Food and Drug Administration-approved for in-hospital and extended thromboprophylaxis in medically ill patients and provide net clinical benefit in these key subgroups. Coronavirus disease-2019 may predispose patients to VTE due to excessive inflammation, platelet activation, endothelial dysfunction, and hemostasis. The optimum preventive strategy for these patients requires further investigation. This article aims to review the latest concepts in predicting and preventing VTE and discuss the new era of extended thromboprophylaxis in hospitalized medically ill patients.

Topics: Anticoagulants; Benzamides; COVID-19; Critical Care; Decision Support Systems, Clinical; Duration of Therapy; Hospitalization; Humans; Medical Informatics; Patient Discharge; Pulmonary Embolism; Pyridines; Risk Assessment; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE), which is characterized by pulmonary embolism and deep vein thrombosis, has become a serious public concern. Notably, over half of the patients with VTE are over 70 years of age, but elderly patients are at high risk of anti-coagulation and bleeding, which increase with age. Moreover, risk factors and frailty also show a difference between elderly patients and ordinary patients diagnosed with VTE. Rivaroxaban is a direct inhibitor of activated factor Xa and has the advantage of predictable pharmacodynamics and pharmacokinetics, no coagulation monitoring, and few drug interactions. As a first-line therapy for VTE, this drug is more advantageous than traditional therapy and exhibits good efficacy and safety for ordinary patients. However, the effectiveness and safety of rivaroxaban in elderly patients have not been fully elucidated. This article reviewed the use of rivaroxaban in elderly patients, including drug interactions, monitoring, reversal agents of rivaroxaban, and the use of small dosages of rivaroxaban in elderly patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for stroke prevention in atrial fibrillation (AF) and the treatment and prevention of venous thromboembolism. There is an issue with safety, especially in clinically relevant bleeding. We performed a network meta-analysis to evaluate the risk of major gastrointestinal (GI) bleeding associated with NOACs.. Interventions were warfarin, enoxaparin, apixaban, dabigatran, edoxaban, and rivaroxaban. The primary outcome was the incidence of major GI bleeding. A subgroup analysis was performed according to the following indications: AF, deep venous thrombosis/pulmonary embolism, and postsurgical prophylaxis.. A total of 29 randomized controlled trials (RCTs) and 4 large observation population studies were included. Compared with warfarin, apixaban showed a decreased the risk of major GI bleeding (relative risk [RR] 0.54, 95% confidence interval [CI] 0.25-0.76), and rivaroxaban tended to increase this risk (RR 1.40, 95% CI 1.06-1.85). Dabigatran (RR 1.25, 95% CI 0.98-1.60), edoxaban (RR 1.07, 95% CI 0.69-1.65), and enoxaparin (RR 1.24, 95% CI 0.63-2.43) did not significantly increase the risk of GI bleeding than did warfarin. In the subgroup analysis, according to indications, apixaban showed a decreased risk of major GI bleeding (RR 0.50, 95% CI 0.34-0.74) than did warfarin in AF studies. Dabigatran (RR 2.36, 95% CI 1.55-3.60, and rivaroxaban (RR 1.75, 95% CI 1.10-6.41) increased the risk of major GI bleeding than did apixaban. An analysis of studies on venous thromboembolism or pulmonary embolism showed that no individual NOAC or enoxaparin was associated with an increased risk of major GI bleeding compared to warfarin.. Individual NOACs had varying profiles of GI bleeding risk. Results of analyses including only RCTs and those including both RCTs and population studies showed similar trends, but also showed several differences.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Enoxaparin; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Network Meta-Analysis; Observational Studies as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007.. To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA.. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019.. We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status.. Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence.. This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GC. There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.

Topics: Adult; Anticoagulants; Arthroscopy; Aspirin; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Knee Joint; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Stockings, Compression; Venous Thrombosis

Venous thrombotic events frequently complicate major elective arthroplasties such as hip and knee replacements. The risk of proximal deep vein thrombosis and pulmonary embolism is estimated at 5 %. For decades, the use of low-dose heparins for up to 5 weeks post-surgery has helped to reduce the risk of thrombotic complications. In this narrative review, we describe the evidence supporting the use of direct oral anticoagulants (in Switzerland - rivaroxaban and apixaban), whose risk-benefit ratios appears superior to that of heparins, at a lower cost. Hybrid strategies combining a short-term anticoagulant followed by low-dose aspirin are also recommended for patients deemed at low thrombotic risk.. Les thromboses veineuses profondes proximales et les embolies pulmonaires sont des complications redoutées après des interventions électives majeures en chirurgie orthopédique (prothèses totales de la hanche et du genou), avec une incidence cumulée estimée à 5 %. Depuis des décennies, ce risque est réduit par l’utilisation d’héparine à dose préventive jusqu’à 5 semaines postopératoires. Dans cette revue narrative, nous décrivons les évidences motivant l’utilisation des anticoagulants oraux directs (rivaroxaban et apixaban en Suisse) qui semblent présenter un rapport bénéfice-risque supérieur aux héparines, à un coût moindre. Des stratégies hybrides comprenant un anticoagulant puis l’aspirine sont désormais également recommandées chez des patients considérés à bas risque thrombotique.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Heparin; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

To assess the efficacy and safety of venous thromboembolism prophylaxis in people undergoing elective total hip replacement.. Systematic review and Bayesian network meta-analyses of randomized controlled trials were conducted for 3 outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding (MB). MEDLINE, EMBASE, and Cochrane Library (CENTRAL) databases were searched. Study quality was assessed using the Cochrane risk-of-bias checklist. Fixed- and random-effects models were fitted and compared. The median relative risk (RR) and odds ratio (OR) compared with no prophylaxis, with their 95% credible intervals (CrIs), rank, and probability of being the best, were calculated.. Forty-two (n = 24 374, 26 interventions), 30 (n = 28 842, 23 interventions), and 24 (n = 31 792, 15 interventions) randomized controlled trials were included in the DVT, PE, and MB networks, respectively. Rivaroxaban had the highest probability of being the most effective intervention for DVT (RR 0.06 [95% CrI 0.01-0.29]). Strategy of low-molecular-weight heparin followed by aspirin had the highest probability of reducing the risk of PE and MB (RR 0.0011 [95% CrI 0.00-0.096] and OR 0.37 [95% CrI 0.00-26.96], respectively). The ranking of efficacy estimates across the 3 networks, particularly PE and MB, had very wide CrIs, indicating high degree of uncertainty.. A strategy of low-molecular-weight heparin given for 10 days followed by aspirin for 28 days had the best benefit-risk balance, with the highest probability of being the best on the basis of the results of the PE and MB network meta-analyses. Nevertheless, there is considerable uncertainty around the median ranks of the interventions.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Bayes Theorem; Cost-Benefit Analysis; Elective Surgical Procedures; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Patient Preference; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Venous Thromboembolism

Prophylactic anticoagulant therapy is recommended to reduce the risk of venous thromboembolism (VTE) after total hip or knee arthroplasty, and has become the standard of care. Rivaroxaban is a novel oral medication that directly inhibits factor Xa for the prevention and treatment of thromboembolic conditions.. A meta-analysis of randomized controlled trials (RCTs) was performed to determine the efficacy and safety of rivaroxaban after total hip arthroplasty (THA) and total knee arthroplasty (TKA) surgery. We reviewed several databases including PubMed, the Cochrane Library, Embase and the US trial registry to detect appropriate RCTs for our meta-analysis. The primary efficacy outcome of this meta-analysis was the combination of any deep-vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and death from any cause. The main safety outcome was bleeding events which included significant bleeding events, clinically relevant insignificant bleeding events, or minor events. Other end points were the number of patients who received blood transfusion the volume of transfused whole blood or red blood cells, and the volume of postoperative drainage.. Thirteen RCTs were included in this meta-analysis. This meta-analysis showed that the overall rate of VTE events, DVT, PE, and death were 1%, 6%, < 1% and < 1%, respectively, for patients receiving treatment with rivaroxaban after THA and TKA surgery. The subgroup analysis demonstrated rivaroxaban had more superior effects in THA patients. The pooled analysis of bleeding events showed that the overall rate of major bleeding events, overt bleeding events associated with fall in Hb of > 2 g/DL, clinically overt bleeding events leading to transfusion of > 2 units of blood, clinically overt bleeding events leading to further surgeries, and non-major bleeding events were < 1%, < 1%, < 1%, < 1%, and 3%, respectively.. This is the first systematic review of the literature providing incidence of efficacy and safety outcomes for thromboprophylaxis in THA and TKA patients. Moreover, this meta-analysis showed that rivaroxaban had more superior effect in THA patients.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Pulmonary embolism (PE) is a common life-threatening cardiovascular condition, with an incidence of 23 to 69 new cases per 100,000 people each year. For selected low-risk patients with acute PE, outpatient treatment might provide several advantages over traditional inpatient treatment, such as reduction of hospitalisations, substantial cost savings, and improvements in health-related quality of life. This is an update of the review first published in 2014.. To compare the efficacy and safety of outpatient versus inpatient treatment in low-risk patients with acute PE for the outcomes of all-cause and PE-related mortality; bleeding; adverse events such as haemodynamic instability; recurrence of PE; and patients' satisfaction.. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 26 March 2018. We also undertook reference checking to identify additional studies.. We included randomised controlled trials of outpatient versus inpatient treatment of adults (aged 18 years and over) diagnosed with low-risk acute PE.. Two review authors selected relevant trials, assessed methodological quality, and extracted and analysed data. We calculated effect estimates using risk ratio (RR) with 95% confidence intervals (CIs), or mean differences (MDs) with 95% CIs. We used standardised mean differences (SMDs) to combine trials that measured the same outcome but used different methods. We assessed the quality of the evidence using GRADE criteria.. One new study was identified for this 2018 update, bringing the total number of included studies to two and the total number of participants to 451. Both trials discharged patients randomised to the outpatient group within 36 hours of initial triage and both followed participants for 90 days. One study compared the same treatment regimens in both outpatient and inpatient groups, and the other study used different treatment regimes. There was no clear difference in treatment effect for the outcomes of short-term mortality (30 days) (RR 0.33, 95% CI 0.01 to 7.98, P = 0.49; low-quality evidence), long-term mortality (90 days) (RR 0.98, 95% CI 0.06 to 15.58, P = 0.99, low-quality evidence), major bleeding at 14 days (RR 4.91, 95% CI 0.24 to 101.57, P = 0.30; low-quality evidence) and at 90 days (RR 6.88, 95% CI 0.36 to 132.14, P = 0.20; low-quality evidence), minor bleeding (RR 1.08, 95% CI 0.07 to 16.79; P = 0.96, low-quality evidence), recurrent PE within 90 days (RR 2.95, 95% CI 0.12 to 71.85, P = 0.51, low-quality evidence), and participant satisfaction (RR 0.97, 95% CI 0.90 to 1.04, P = 0.39; moderate-quality evidence). We downgraded the quality of the evidence because the CIs were wide and included treatment effects in both directions, the sample sizes and numbers of events were small, and because the effect of missing data and the absence of publication bias could not be verified. PE-related mortality, and adverse effects such as haemodynamic instability and compliance, were not assessed by the included studies.. Currently, only low-quality evidence is available from two published randomised controlled trials on outpatient versus inpatient treatment in low-risk patients with acute PE. The studies did not provide evidence of any clear difference between the interventions in overall mortality, bleeding and recurrence of PE.

Topics: Acute Disease; Adult; Ambulatory Care; Anticoagulants; Confidence Intervals; Enoxaparin; Hemorrhage; Hospitalization; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban

Pulmonary embolism (PE) is the most feared clinical presentation of venous thromboembolism (VTE). Patients with PE have traditionally been treated in hospital; however, many are at low risk of adverse outcomes and current guidelines suggest outpatient treatment as an option. Outpatient treatment of PE offers several advantages, including reduced risk of hospital-acquired conditions and potential cost savings. Despite this, patients with low-risk PE are still frequently hospitalized for treatment. This narrative review summarizes current guideline recommendations for the identification of patients with low-risk PE who are potentially suitable for outpatient treatment, using prognostic assessment tools (e.g. the Pulmonary Embolism Severity Index [PESI] and simplified PESI) and clinical exclusion criteria (e.g. Hestia criteria) alone or in combination with additional cardiac assessments. Treatment options are discussed along with recommendations for the follow-up of patients managed in the non-hospital environment. The available data on outpatient treatment of PE are summarized, including details on patient selection, anticoagulant choice, and short-term outcomes in each study. Accumulating evidence suggests that outcomes in patients with low-risk PE treated as outpatients are at least as good as, if not better than, those of patients treated in the hospital. With mounting pressures on health care systems worldwide, increasing the proportion of patients with PE treated as outpatients has the potential to reduce health care burdens associated with VTE.

Topics: Administration, Oral; Anticoagulants; Cardiology; Drug Approval; Hemodynamics; Hospitalization; Humans; Length of Stay; Outpatients; Practice Guidelines as Topic; Prognosis; Pulmonary Embolism; Pyrazoles; Pyridones; Risk; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

: Rivaroxaban, a direct oral anticoagulant, is widely used for the treatment of venous thromboembolism (VTE) in adult patients. The approval of rivaroxaban for the treatment of deep vein thrombosis and pulmonary embolism and the extended secondary prevention of recurrent VTE is based on the results of the EINSTEIN DVT and EINSTEIN PE trials, and the EINSTEIN EXT and EINSTEIN CHOICE trials, respectively. This review provides an updated overview of these completed EINSTEIN studies in adult patients, including results of subanalyses in patients at high risk of recurrent VTE, and discusses the emerging data from the EINSTEIN Junior programme, which is evaluating the use of rivaroxaban for the treatment of paediatric VTE. In the EINSTEIN DVT and EINSTEIN PE trials, rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily thereafter) was shown to be an effective and safe alternative to standard anticoagulation for the treatment of deep vein thrombosis and pulmonary embolism in a broad range of adult patients. These results are supported by increasing amounts of real-world data from patients treated with rivaroxaban in routine clinical practice worldwide. In the EINSTEIN EXT and EINSTEIN CHOICE trials, rivaroxaban was superior to placebo and acetylsalicylic acid, respectively, for the extended treatment of VTE - physicians can now choose between two doses of rivaroxaban (20 mg once daily or 10 mg once daily) for the extended prevention of recurrent VTE, based on a patient's risk of recurrence, bleeding and personal preferences.

Topics: Adult; Aspirin; Child; Clinical Trials as Topic; Humans; Precision Medicine; Pulmonary Embolism; Rivaroxaban; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis

Previous clinical trials have addressed that rivaroxaban is effective for the treatment of patients with pulmonary embolism (PE). This study will systematically assess its efficacy and safety for PE.. We will carry out this study by searching the following electronic databases from inception to March 1, 2019 without language restrictions: Cochrane Library, EMBASE, PUBMED, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. In addition, we will also search clinical trial registries, dissertations, and conference abstracts to avoid any missing potential studies. All randomized controlled trials of rivaroxaban for patients with PE will be fully considered. Two researchers will independently perform literature selection, data collection, and methodological quality assessment. If it is appropriate, outcome data will be pooled by using a fixed-effect model or random-effect model, and meta-analysis will be considered for operation.. All efficacy and safety of rivaroxaban for PE will be assessed through all primary and secondary outcomes. The primary outcomes are all-cause mortality and major bleeding. The secondary outcomes are recurrent venous thromboembolism, duration of hospital stay, quality of life, patient satisfaction, and adverse events.. The findings of this study will summarize updated evidence on the efficacy and safety of rivaroxaban for patients with PE.. It is not necessary to inquire ethical approval for this study, because it will not analyze any individual patient data. The results of this study will be published through peer-reviewed journals.. PROSPERO CRD42019126095.

Topics: Factor Xa Inhibitors; Humans; Pulmonary Embolism; Rivaroxaban

Acute pulmonary embolism (PE) is a relatively common cardiopulmonary emergency that is a major cause of hospitalization and morbidity and is the primary cause of mortality associated with venous thromboembolism (VTE). During the last decade, one of the biggest changes in the management of PE has been the approval of four non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) for the treatment of PE and deep vein thrombosis and secondary prevention of VTE. Areas covered: This article reviews the evolving management of PE in the NOAC era and addresses three fundamental questions: who should receive NOACs over conventional heparin/vitamin K antagonist regimens for the treatment of acute PE; should patients be treated as inpatients or outpatients; and how long should patients be treated to reduce the risk of recurrence? Expert commentary: The management of PE is changing. NOACs provide new anticoagulant treatment options for patients with PE, based on Phase III clinical study results. The consistent efficacy and safety profile of NOACs across many PE patient subgroups, including the elderly, fragile patients, those with active cancer and high-risk (right ventricular dysfunction) patients, suggests NOAC use will increase among these patients.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism

Topics: Ambulatory Care; Anticoagulants; Dabigatran; Female; Hemorrhage; Humans; Length of Stay; Male; Neoplasms; Patient Discharge; Patient Selection; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Severity of Illness Index; Substance Abuse, Intravenous; Thiazoles

In the EINSTEIN-Pulmonary Embolism (PE) trial, subjects randomized to rivaroxaban versus enoxaparin bridging to vitamin K antagonist (VKA) therapy experienced a reduced index hospital length of stay (LOS). We sought to conduct a systematic review of real-world studies comparing LOS, costs and early outcomes among patients treated with rivaroxaban or parenterally bridged VKA in routine practice.. We searched Medline and Scopus from 1 January 2011 to 30 November 2016 to identify observational studies comparing acute PE patients anticoagulated with rivaroxaban or parenterally bridged VKA and reporting data on index hospital LOS, costs and/or early post-PE outcomes. Studies not using appropriate methods for minimizing confounding bias or not published in English were excluded.. Five studies met inclusion criteria. Rivaroxaban use was associated with decreased index hospital LOS (range: 1.36-1.70 days) and treatment costs (range: $1818-$2688) during an index stay compared to parenterally bridged warfarin. No differences in early readmission for recurrent thrombosis were noted between anticoagulation strategies. Readmission for major bleeding was rare in both cohorts. Similar reductions in LOS (range: 0.23-4.3 days) and costs (range: $251-$7094) were observed with rivaroxaban in studies restricted to patients deemed low risk for early complications by clinical gestalt or by a clinical- or claims-based risk stratification tool.. Regardless of patient predicted risk of post-PE complications, real-world studies suggest that rivaroxaban is associated with a reduced hospital LOS and costs versus parenterally bridged warfarin, without increasing readmission.

Topics: Anticoagulants; Enoxaparin; Health Care Costs; Hemorrhage; Humans; Length of Stay; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Warfarin

After arthroplasty treatment, some complications commonly occur, such as early revision, infection/dislocation, and venous thromboembolism (VTE). This study aims to use a network meta-analysis to compare effects of 9 anticoagulant drugs (edoxaban, dabigatan, apixaban, rivaroxaban, warfarin, heparin, bemiparin, ximelagatran, and enoxaparin) in preventing postoperative complications in arthroplasty patients.. After retrieving PubMed, Embase, and Cochrane Library database from the inception to November 2016, randomized controlled trials were enrolled. The integration of direct and indirect evidences was performed to calculate odd ratios and the surface under the cumulative ranking curves. Nineteen eligible randomized controlled trials were included.. The network meta-analysis results showed that compared with warfarin, edoxaban, apixaban, and rivaroxaban had a lower incidence rate in asymptomatic deep venous thrombosis, which indicated that edoxaban, apixaban, and rivaroxaban had better effects on prevention. Similarly, in comparison to enoxaparin, edoxaban and rivaroxaban had better effect; rivaroxaban was better than ximelagatran in preventive effects. Compared with apixaban, edoxaban, dabigatan, rivaroxaban, and enoxaparin had a higher incidence rate in clinically relevant non-major bleeding, which showed that preventive effects were relatively poor. In addition, the results of the surface under the cumulative ranking curves showed that rivaroxaban and bemiparin worked best on symptomatic deep venous thrombosis and pulmonary embolism. In terms of bleeding, apixaban and warfarin had better preventive effects.. Our findings suggested that rivaroxaban may work better in terms of symptomatic deep venous thrombosis and pulmonary embolism, whereas apixaban had better preventive effects in bleeding.

Topics: Anticoagulants; Arthroplasty; Azetidines; Benzylamines; Dabigatran; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism; Warfarin

Pulmonary embolism (PE) affects >600,000 patients per year in the United States. Evaluation includes clinical decision rules, laboratory tests, and several imaging modalities. The diagnosis of PE has risen in recent years, particularly subsegmental PE (SSPE). Controversy exists concerning the diagnosis and treatment of these lesions.. We sought to provide emergency physicians with a review of the controversies surrounding PE testing and the diagnosis and treatment of SSPE.. With the rise of computed tomography (CT) testing for PE, diagnosis has increased. Providers often omit risk stratification in favor of D-dimer or imaging, which does not have literature support. The detection of PE has risen by 80%, and this increased testing is associated with several risks, including contrast reaction, nephropathy, and increased radiation. SSPE diagnosis has risen with improved imaging technology, but the literature shows low interobserver agreement with diagnosis of true SSPE. Studies disagree on the clinical significance and dangers of this PE subset. The American College of Chest Physicians 2016 guidelines recommend withholding anticoagulation for SSPE with low risk for recurrent thrombus and no concurrent deep vein thrombosis. Patients at high risk for recurrent venous thromboembolism or with deep vein thrombosis warrant anticoagulation. The provider is ultimately responsible for appropriate evaluation with risk stratification and selective testing.. SSPE presents a quandary, because the literature differs in showing harm despite increased diagnosis. American College of Chest Physicians guidelines for the treatment of SSPE take into account the patient, the imaging, and other imaging modalities. Providers should use risk stratification with shared decision-making in the evaluation and treatment of SSPE.

Topics: Anticoagulants; Dabigatran; Decision Making; Humans; Patient Outcome Assessment; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles; Tomography, X-Ray Computed; Venous Thromboembolism

Emergency physicians make treatment decisions in patients who present to the emergency department (ED) with acute venous thromboembolism (VTE). They also encounter patients on target-specific oral anticoagulants (TSOACs) who require urgent intervention. New approvals and increasing prescriptions for TSOACs (e.g., apixaban, dabigatran, edoxaban, and rivaroxaban) for the management of several thromboembolic disorders warrant an evaluation of the impact of these agents in the ED setting.. This review discusses the use of TSOACs in the ED for the treatment of acute VTE, and highlights strategies for the management of patients on TSOACs who present to the ED with other complications, such as bleeding complications or requiring emergency surgery.. Apixaban, dabigatran, edoxaban, and rivaroxaban have been approved for the treatment of acute VTE. We discuss the impact of this on ED management of TSOAC-naïve patients and highlight results with TSOACs in high-risk subgroups including the elderly and those with prior VTE or active cancer. This review also discusses management strategies for patients on TSOACs. For emergency physicians, strategies for the management of bleeding, approaches to patient care when emergency surgery is needed, laboratory assays for measuring plasma concentrations of TSOACs, and drug-drug interactions are of special importance.. Familiarity with TSOACs will better position emergency physicians to provide state-of-the art care to their patients with VTE and help them manage potentially complicated circumstances related to the chronic use of these drugs.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Blood Coagulation Tests; Dabigatran; Drug Interactions; Drug Monitoring; Emergency Service, Hospital; Factor Xa Inhibitors; Hemorrhage; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products.. Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information.. Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions.. The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy.. The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Drug Interactions; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Male; Middle Aged; Phlebography; Prognosis; Pulmonary Embolism; Pyridines; Randomized Controlled Trials as Topic; Rivaroxaban; Severity of Illness Index; Survival Analysis; Thiazoles; Treatment Outcome; Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) is a life or limb-threatening thrombotic thrombocytopenia. HIT is traditionally treated with factor-IIa inhibitors such as bivalirudin, lepirudin, or argatroban. However, these agents usually require parenteral administration and are not generally available in all countries. Recently, several experiences with novel oral anticoagulants (NOACs) administration to treat HIT had been reported. NOACs generally offer advantages such as consistent and predictable anticoagulation, oral administration with good patient compliance, and a good safety profile. We report a case of HIT with severe thrombotic complications successfully treated with rivaroxaban and discuss the current knowledge about the use of NOACs for the treatment of this potentially fatal thrombocytopenia.

Topics: Anticoagulants; Diagnosis, Differential; Factor Xa Inhibitors; Female; Heparin; Humans; Middle Aged; Pulmonary Embolism; Rivaroxaban; Thrombocytopenia; Treatment Outcome; Venous Thrombosis

A healthy female presented with upper extremity (UE) swelling of several days duration. Admission laboratories were normal except for an elevated D-dimer. An UE ultrasound with Doppler revealed a thrombus in the right subclavian vein. A subsequent chest CT angiogram further characterised the subclavian vein thrombus and also identified a pulmonary embolus. A thorough history and laboratory evaluation showed that her only risk factors were long-time contraceptive pills and a recent cycle of ovarian hyperstimulation (OH) 7 weeks prior to presentation. Anticoagulation treatment was started and the patient's remaining outpatient work-up was negative for all other hereditary causes. A complete anatomic work-up showed bilateral thoracic outlet syndrome (TOS). A review of the literature on the occurrence of upper extremity deep venous thrombosis suggests that these usually occur in the presence of a predisposing factor, including catheters, indwelling devices and active malignancies. OH has been shown to precipitate venous thromboembolism events; however, the diagnosis of bilateral TOS as a predisposing risk factor has not been described in a patient who had recently undergone recent OH and in one who was not actively pregnant.

Topics: Adult; Computed Tomography Angiography; Diagnosis, Differential; Factor Xa Inhibitors; Female; Humans; Ovulation Induction; Pulmonary Embolism; Rivaroxaban; Subclavian Vein; Ultrasonography, Doppler, Color; Upper Extremity Deep Vein Thrombosis

Traditional anticoagulants, such as low-molecular-weight heparin and vitamin K antagonists, have been the mainstay for the treatment of venous thromboembolism (VTE) in the hospital setting and after discharge. These anticoagulants are effective but are associated with some limitations that may lead to their underuse. Based on the results of the EINSTEIN clinical trial program, the oral, direct factor Xa inhibitor rivaroxaban is approved for the treatment of acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and for the prevention of recurrent VTE. The single-drug approach with rivaroxaban is now available in both the hospital and the outpatient settings and may overcome some of the limitations of traditional agents. This review provides hospital physicians with an overview of the practical management of rivaroxaban and a critical evaluation of its use for the treatment of DVT and PE, including in specific clinical settings and special patient populations.

Topics: Factor Xa Inhibitors; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Four target-specific oral anticoagulants (TSOA's) have been compared to a vitamin K antagonist for the treatment of acute venous thromboembolism (VTE): dabigatran (D), rivaroxaban (R), apixaban (A) and edoxaban (E). We performed an indirect comparison of the TSOA's, based on the six phase III trials identified (RE-COVER I, RE-COVER II, EINSTEIN-DVT, EINSTEIN-PE, AMPLIFY and Hokusai-VTE). There was no statistically significant difference in risk of recurrent VTE or all-cause mortality between the TSOA's. For major bleeding, the RR of an event was 0.42 (95% CI 0.21-0.87, p = 0.02) for A versus D, compared with 0.57 (95% CI 0.29-1.15, p = 0.12) for A versus R, 0.37 (95% CI 0.19-0.73, p < 0.001) for A versus E, 0.74 (95% CI 0.42-1.30, p = 0.30) for R versus D, 0.64 (95% CI 0.38-1.08, p = 0.10) for R versus E and 1.15 (95% CI 0.66-2.00, p = 0.62) for E versus D. For the composite endpoint of major or clinically relevant nonmajor bleeding, the RR was 0.71 (95% CI 0.53-0.96, p = 0.02) for A versus D, 0.47 (95% CI 0.37-0.61, p < 0.001) for A versus R, 0.54 (95% CI 0.42-0.70, p < 0.001) for A versus E, 1.50 (95% CI 1.17-1.92, p = 0.001) for R versus D, 1.15 (95% CI 0.95-1.39, p = 0.16) for R versus E and 1.31 (95% CI 1.02-1.68, p = 0.04) for E versus D. Overall, apixaban appears to be associated with a lower risk of bleeding than the other TSOA's. This analysis may be helpful to the clinician in trying to balance risk versus benefit in selecting a new anticoagulant. A dedicated randomized trial directly comparing the new agents would be required to confirm these results.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Recurrence; Risk Assessment; Rivaroxaban; Survival Analysis; Thiazoles; Venous Thrombosis

A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and safety of direct factor Xa inhibitors (rivaroxaban and apixaban) with enoxaparin for the prevention of venous thromboembolism (VTE) after total knee replacement.. A systematic literature search in Medline, EMBASE, EBSCO, Springer, Ovid and Cochrane library databases was performed to identify RCTs comparing rivaroxaban/apixaban with enoxaparin for the prevention of VTE after total knee replacement. The outcomes including deep vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding were pooled using risk ratios (RRs) with their 95% confidence intervals (95% CIs) as statistic.. A total of 6 RCTs with 13,790 patients were included in this meta-analysis. Overall, the incidence of DVT was significantly decreased with the use of direct Xa inhibitors (both twice daily [b.i.d] and once daily [q.d.] regimes) comparing with the enoxaparin treatment (P<0.01); however, there was no significant influencing difference between direct Xa inhibitors (b.i.d. regime) and enoxaparin on the incidence of PE (P=0.06), while significantly lower rate was found for q.d. regime of direct Xa inhibitors (P=0.02). With respect to major bleeding, the pooled analysis did not demonstrate a significant difference between direct Xa inhibitors (b.i.d. and q.d. regimes) and enoxaparin (30mg and 40mg b.i.d.).. In conclusion, our results confirmed that direct Xa inhibitors (rivaroxaban and apixaban) were more effective for prevention of VTE after total knee replacement as compared with enoxaparin, without increasing major bleeding risk.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The incidence of post-operative arterial thrombosis (AT) (acute myocardial infarction [AMI] and ischaemic stroke) is increased in patients undergoing total hip replacement (THR) or total knee replacement (TKR). We compared the incidence of post-operative AT in non-vitamin K antagonist oral anticoagulants (NOACs)-treated and enoxaparin-treated patients, performing a systematic review of phase III randomised controlled trials (RCTs) of venous thromboembolism (VTE) prophylaxis in THR and TKR. Studies were identified by electronic search of MEDLINE and EMBASE database until July 2014. Differences between NOACs and enoxaparin groups in the efficacy and safety outcomes were expressed as odds ratios (ORs) with pertinent 95 % confidence intervals (95 % CI). Statistical heterogeneity was assessed with the I² statistic. Eleven phase III RCTs for a total of 31,319 patients were included. Patients underwent TKR in six studies and THR in five studies. The NOACs under study were dabigatran (four studies), apixaban (three studies) and rivaroxaban (four studies). AT occurred in 0.23 % of patients on NOACs and in 0.27 % of patients on enoxaparin: the OR at fixed-effect model was 0.86 (95 % CI 0.53-1.40; I² 11 %). No differences in AT incidence among the three NOACs were observed. The incidence of major and clinically relevant bleeding was similar in NOACs and enoxaparin groups (OR 1.03, 95 % CI 0.92-1.15; I² 38 %). In conclusion, in RCTs of pharmacological VTE prophylaxis in patients undergoing THR or TKR, there was no difference in the incidence of post-operative AT among patients treated with NOACs, compared to those treated with enoxaparin.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Brain Ischemia; Clinical Trials, Phase III as Topic; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Postoperative Complications; Postoperative Hemorrhage; Prothrombin; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome

A number of direct oral anticoagulants are now available and offer alternative strategies for anticoagulation therapy. Rivaroxaban, a direct oral Factor Xa inhibitor, is approved for use across several thromboembolic indications. This article aims to provide an overview of the key pharmacological characteristics of rivaroxaban and the rationale and evidence for the use of different dose regimens across its licenced indications, and offer practical guidance to healthcare professionals on responsible use. References were sourced via PubMed searches using the search string (rivaroxaban AND (pharmacokinetics OR pharmacodynamics OR (clinical studies) OR (drug interaction)) NOT review NOT (children OR pediatrics OR paediatrics OR adolescent)).. Rivaroxaban exhibits predictable pharmacokinetics and pharmacodynamics, and thus does not require routine coagulation monitoring, unlike vitamin K antagonists (e.g. warfarin). Rivaroxaban also has a lower potential for drug-drug and food-drug interactions compared with warfarin; however, co-administration with strong inhibitors of both cytochrome P450 3A4 and P-glycoprotein is not recommended. The data indicate that dose adjustment is not necessary for age, gender or body weight. The dosing regimens of rivaroxaban vary depending on the indication, and phase III studies have demonstrated a favourable benefit-risk profile of rivaroxaban compared with traditional standard of care.. Rivaroxaban may offer an anticoagulant option that could simplify and improve the management of patients with thromboembolic disorders.

Topics: Administration, Oral; Anticoagulants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Clinical Trials as Topic; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Interactions; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Rivaroxaban; Thromboembolism; Venous Thrombosis

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Contraindications; Dabigatran; Drug Interactions; Humans; International Normalized Ratio; Male; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thiophenes; Venous Thromboembolism

A short cut review was carried out to establish whether Rivaroxaban is superior to warfarin in the management of pulmonary embolism. Three studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that Rivaroxaban is a promising alternative to warfarin in the management of pulmonary embolism.

Topics: Anticoagulants; Evidence-Based Emergency Medicine; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Rivaroxaban; Warfarin

The treatment of pulmonary embolism is going to be deeply modified by the development of Direct Oral Anticoagulants (DOACs). There are currently three anti-Xa factors (rivaroxaban, apixaban, edoxaban) and one anti-IIa factor (dabigatran) labeled by the FDA and the EMA. All these drugs are direct anticoagulant, orally effective, without the need for adaptation to hemostasis test. As kidney excretion is involved for all of them, they are contra-indicated in patients with severe renal failure (creatinine clearance < 30 mL/min according to Cockcroft & Gault formula). All the anti-Xa factor drugs are metabolized by liver cytochromes and then contra-indicated in case of liver insufficiency. Of note, the four DOACS have been evaluated in non-inferiority trials, including one open-label trial (the EINSTEIN program with the rivaroxaban). Moreover, two of them (rivaroxaban and apixaban) were evaluated in a single drug approach (provided initial increased doses: 15 mg bid during 21 days for rivaroxaban and 10 mg bid during 7 days for apixaban) whereas the two others (edoxaban and dabigatran) were evaluated after at least 5 days of parenteral heparin. They were found to be non-inferior to the conventional treatment, but also seem to be associated with a decreased risk of major bleeding, in a quite young and without significant comorbidities population. The risk/benefit ratio of DOACs in specific subgroups deserves prospective validations.

Topics: Antithrombins; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Thiazoles; Venous Thromboembolism

Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism.. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism.. The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations.. We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism.. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI).. We included five randomised controlled trials with a total of 7897 participants. Two studies tested oral DTIs (dabigatran) and three studies tested oral factor Xa inhibitors (one rivaroxaban, one edoxaban and one apixaban).Analysis showed no difference in the effectiveness of oral DTIs and standard anticoagulation in preventing recurrent pulmonary embolism (OR 1.02, 95% CI 0.50 to 2.04; two studies; 1602 participants; high quality evidence), recurrent venous thromboembolism (OR 0.93, 95% CI 0.52 to 1.66; two studies; 1602 participants; high quality evidence), deep vein thrombosis (DVT) (OR 0.79, 95% CI 0.29 to 2.13; two studies; 1602 participants; high quality evidence) and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; two studies; 1527 participants; high quality evidence).For oral factor Xa inhibitors, when we combined the three included studies together in meta-analyses, there was significant heterogeneity for recurrent pulmonary embolism (OR 1.08, 95% CI 0.46 to 2.56; two studies; 4509 participants; I(2) = 58%; moderate quality evidence). The oral factor Xa inhibitors were no more or less effective in the prevention of recurrent venous thromboembolism (OR 0.85, 95% CI 0.63 to 1.15; three studies; 6295 participants; high quality evidence), DVT (OR 0.72, 95% CI 0.39 to 1.32; two studies; 4509 participants; high quality evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; one study; 4817 participants; moderate quality evidence) or major bleeding (OR 0.97, 95% CI 0.59 to 1.62; two studies; 4507 participants; high quality evidence). None of the studies measured quality of life.. Moderate to high quality evidence suggests that there are no differences between DOACs and standard anticoagulation for the long-term treatment of pulmonary embolism, for the outcomes recurrent pulmonary embolism, recurrent venous thromboembolism, DVT, all-cause mortality and major bleeding.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Dabigatran; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Dabigatran (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (direct activated factor X inhibitors) are increasingly being used in clinical practice. Compared with vitamin K antagonists, they are more convenient, do not require laboratory monitoring, have limited drug and food interactions, and have fixed dosages suitable for most patients. But the shortcomings of these agents can jeopardize their efficacy and increase the risk of bleeding. Their future role in preventing and treating thromboembolic disease will depend on building clinical experience, but current evidence indicates that they are reasonable alternatives to vitamin K antagonists.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thrombosis

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode.

Topics: Age Factors; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Dabigatran; Disease Management; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fondaparinux; Humans; Male; Morpholines; Obesity; Polysaccharides; Postthrombotic Syndrome; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Sex Factors; Thiophenes; Thrombophilia; Ultrasonography; Venous Thromboembolism; Venous Thrombosis; Warfarin

Rivaroxaban (Xarelto(®)), an oral direct factor Xa inhibitor, is approved for the initial treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as the prevention of recurrent DVT and PE. It is administered at a fixed oral dose and does not require routine coagulation monitoring. In the EINSTEIN-DVT and EINSTEIN-PE trials, in over 8,000 patients with DVT and/or PE, a single-drug approach with rivaroxaban was shown to be noninferior to standard therapy consisting of subcutaneous enoxaparin sodium overlapping with and followed by an oral dose-adjusted vitamin K antagonist (enoxaparin-VKA) with regard to the incidence of symptomatic recurrent venous thromboembolism (VTE) after 3, 6 or 12 months of treatment. Rivaroxaban was generally well tolerated in patients with DVT or PE, with no significant between-group differences in clinically relevant bleeding between the rivaroxaban and enoxaparin-VKA groups. Notably, rivaroxaban was associated with a significantly lower rate of major bleeding compared with enoxaparin-VKA when EINSTEIN-DVT and EINSTEIN-PE data were pooled. Pharmacoeconomic analyses indicated that rivaroxaban may be a cost-effective alternative to enoxaparin-VKA for the treatment of DVT or PE and prevention of recurrent VTE. Extended prophylaxis with rivaroxaban reduced the incidence of symptomatic recurrent VTE to a greater extent than placebo in the EINSTEIN-Extension trial, but was associated with a non-significant increase in the risk of clinically relevant bleeding compared with placebo. In conclusion, rivaroxaban is a reasonable alternative to standard therapy for the treatment of DVT and PE, and as extended thromboprophylaxis.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Direct oral anticoagulants (DOACs) specifically target factor IIa or Xa and represent a major step forward in the treatment of acute- and long-term prevention of venous thrombo-embolism (VTE). They are at least as effective and as safe as conventional therapy (heparins and vitamin-K inhibitors) and have practical advantages, such as fixed dosing and no need for laboratory monitoring. These antithrombotic agents introduce a new paradigm for the day-to-day management of VTE. Direct oral anticoagulants should streamline the management of most patients with VTE and will facilitate care in the outpatient setting. Nevertheless, it remains uncertain how to select specific DOACs for particular profiles of patients, and the optimal management of bleeding complications is evolving.

Topics: Acute Disease; Administration, Oral; Antithrombins; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Long-Term Care; Morpholines; Perioperative Care; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

The introduction of factor Xa inhibitors advocated the initiation of clinical trials that addressed the value of anticoagulation in patients with hemodynamically stable primary pulmonary embolism (PE). In the Matisse trial in patients with PE, fondaparinux administered at therapeutic doses followed by vitamin K antagonists (VKA) has shown a comparable efficacy and safety profile to that seen with intravenous adjusted-dose unfractionated heparin/VKA. A long-acting derivative of fondaparinux, idraparinux, failed to achieve similar results. On the other hand, the Cassiopea study revealed that once weekly injections of idrabiotaparinux, a slightly modified form of idraparinux, have similar efficacy and better safety profile compared to VKAs in the long-term treatment of patients with PE. However, the inconvenient parenteral administration of both fondaparinux and idrabiotaparinux limits their routine clinical use. The availability of antithrombotic compounds that can be administered orally in fixed dose, owing to their predictable pharmacokinetics and pharmacodynamics, and have a lower potential for drug and food interactions has opened new horizons for the treatment of patients with PE. The Einstein PE, Amplify and Hokusai studies, conducted with rivaroxaban, apixaban and edoxaban, respectively, showed that for the treatment of PE they possess a more favorable benefit-to-risk profile than the conventional antithrombotic drugs. In addition, rivaroxaban and apixaban make it possible to treat uncomplicated PE patients from the beginning, without the need for the parenteral administration of heparins or fondaparinux, and edoxaban allows the treatment of fragile patients with lower doses. All of them cover a wide spectrum of clinical presentations, including PE patients at intermediate risk.

Topics: Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Pulmonary Embolism; Rivaroxaban

To systematically examine discontinuation rates with new US Food and Drug Administration-approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation.. Poor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence.. Eighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio [RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators.. Study drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous thromboembolism/pulmonary embolism and prevention of stroke in patients with atrial fibrillation but were worse in acute coronary syndromes as noted in evidence from contemporary RCTs.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Medication Adherence; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) comprises both deep vein thrombosis and pulmonary embolism. VTE is a leading cause of morbidity and mortality worldwide and its increasing incidence and prevalence are a major health concern. The primary medical objective during the acute phase of VTE treatment is to prevent thrombus extension and embolization. Extended treatment aims to prevent or minimize long-term complications, such as recurrent VTE, post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension.. Anticoagulant therapy has been the mainstay of treatment for VTE and traditionally involves initial therapy with heparin, overlapping with and followed by a vitamin K antagonist. Although effective, standard heparin/vitamin K antagonist therapy has several limitations that can be overcome by more recently developed target-specific oral anticoagulants (TSOACs). These agents have predictable pharmacokinetics, a rapid onset of action and few drug-drug or drug-food interactions. Furthermore, TSOACs offer convenient anticoagulation without the need for routine coagulation monitoring and dose adjustment.. The efficacy and safety data from phase III clinical trials support the use of TSOACs for VTE treatment, including in special patient populations. Risk-stratification tools and strategies have been developed to assist physicians in managing anticoagulation treatment.. Rivaroxaban is the first TSOAC to gain widespread approval for the treatment of acute deep vein thrombosis and pulmonary embolism and the long-term prevention of recurrent VTE as monotherapy. Dabigatran has also been approved for this indication recently. TSOACs, especially as monotherapy, represent a paradigm shift in clinical practice for the management of patients with VTE.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Rivaroxaban is a factor Xa inhibitor recently approved for use in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Older adults are at an increased risk for venous thromboembolism (VTE), and rivaroxaban offers an alternative to standard treatment including vitamin K antagonists. This review evaluates the literature supporting this new indication with a focus on the safety and efficacy in older adults as well as those with renal insufficiency and fragility, which the EINSTEIN-PE study defined as those older than 75 years of age, weighing 50 kg or less, or with a creatine clearance (Clcr) of less than 50 mL/min. Three large studies (EINSTEIN-PE, -DVT, -EXT) provide an evaluation of recurrent VTE and bleeding events with the use of rivaroxaban. EINSTEIN-DVT and EINSTEIN-PE showed rivaroxaban to be equivalent to standard treatment in the overall population as well as in older adults and those with renal insufficiency and fragility. Further, EINSTEIN-EXT showed benefit of rivaroxaban over placebo for extended VTE protection (i.e., longer than 6 to 12 months of treatment), both overall and in the subgroups of those older than 75 years of age and with a Clcr of 50 mL/min to < 80 mL/min..

Topics: Aged; Aged, 80 and over; Aging; Factor Xa Inhibitors; Humans; Kidney; Morpholines; Pulmonary Embolism; Recurrence; Renal Insufficiency; Rivaroxaban; Thiophenes; Venous Thromboembolism

Thromboembolic diseases are common. Heparins and the vitamin K antagonists have been the mainstay of therapy for > 60 years, but both classes of agents have limitations. The "ideal" anticoagulant should be as effective and safe as heparin and vitamin K antagonists but should also be available in both a parenteral and an oral formulation, have predictable pharmacokinetics, and lack significant toxicities unrelated to the anticoagulant activity. Moreover, it should target a specific coagulation factor and have an antidote that leads to rapid reversal. There are now agents that fulfill some of these criteria. Here we review the pharmacology and effectiveness of the oral activated factor X inhibitors rivaroxaban and apixaban and the oral direct thrombin inhibitor dabigatran. These agents have undergone extensive phase 3 testing and are currently approved for various indications in the United States, Canada, or Europe. Rivaroxaban is approved in the United States for VTE prevention after major orthopedic surgery and for stroke prevention in atrial fibrillation and is approved in Europe and Canada for secondary prevention of VTE. Apixaban is currently under review by the US Food and Drug Administration for stroke prevention and is approved in Europe for VTE prevention following major orthopedic surgery. Dabigatran is approved in the United States for stroke prevention in nonvalvular atrial fibrillation and is being reviewed for secondary prevention of VTE.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombin

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.

Topics: Administration, Oral; Anticoagulants; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

The management of thromboprophylaxis in patients with pelvic and acetabular fractures remains a highly controversial topic within the trauma community. Despite anticoagulation, venous thromboembolism (VTE) remains the most common cause of surgical morbidity and mortality in this high-risk patient group. Although various thromboprophylactic regimes are employed, evidence relating to the most effective method remains unclear. Controversies surrounding screening, the use of prophylactic inferior vena cava filters (IVCF) and chemothromboprophylaxis in polytraumatised patients, particularly those with pelvic and acetabular fractures, form the basis of considerable debate. With the absence of a well-designed clinical trial and the presence of ongoing controversies within the literature, this review will explore current treatment options available to trauma surgeons and highlight differing scientific opinions, providing an update on the role of screening and current available preventative measures. We cover existing as well as recent advances in chemical thromboprophylactic agents and discuss external mechanical compression devices, the usefulness of serial duplex ultrasonography and the role of extended chemothromboprophylaxis on discharge. The evidence behind prophylactic IVCF is also considered, along with reported complication profiles. We conclude with a proposed protocol for use in major trauma centres, which can form the basis of local policy for the prevention of VTE in trauma patients with pelvic and acetabular fractures.

Topics: Acetabulum; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Coumarins; Dabigatran; Fondaparinux; Fractures, Bone; Heparin; Humans; Mass Screening; Morpholines; Multiple Trauma; Pelvis; Polysaccharides; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Thiophenes; Vena Cava Filters; Venous Thromboembolism

Until recently, warfarin had been one of the only treatment options for long-term anticoagulation of patients with atrial fibrillation, venous thromboembolism, or other medical conditions that require chronic anticoagulation. A main concern when treating patients with anticoagulants is balancing the benefits of preventing a thromboembolic event with the risks of bleeding events. The US Food and Drug Administration recently approved 2 new oral anticoagulants, dabigatran and rivaroxaban, for stroke prevention in patients with atrial fibrillation, and is currently reviewing a drug application for a third new oral anticoagulant, apixaban. These new anticoagulants do not require strict and frequent laboratory monitoring, dosing adjustments, or dietary restrictions, and they incur fewer drug-drug interactions than warfarin. However, these new medications do not have specific reversal agents, may require dosage adjustment based on patient renal function, and lack clinical data regarding their long-term safety and efficacy. The 2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for antithrombotic therapy and prevention of thrombosis include recommendations for dabigatran, rivaroxaban, and apixaban for certain indications. Each of the 3 novel oral anticoagulants has specific pharmacokinetic and pharmacodynamic properties that may make them suitable agents for use in specific patient populations. Knowledge of dosing, drug-drug interactions, monitoring parameters, and clinical considerations for each of these new medications will help clinicians decide for which patients they may be best suited to replace conventional therapy with warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Humans; Morpholines; Postoperative Complications; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis

New oral anticoagulants, acting either as direct factor-Xa or thrombin inhibitors, have been evaluated for the acute and long-term treatment of venous thromboembolism (VTE). Dabigatran and rivaroxaban are as effective as conventional therapy (heparin/vitamin K antagonists) without safety concerns. Rivaroxaban allows a single-drug regimen even in patients with pulmonary embolism, while dabigatran requires 5-7 days of initial heparin treatment. The results of clinical trials with apixaban and edoxaban will become available in the coming months. Rivaroxaban, apixaban and dabigatran are more effective than placebo for the extended treatment of VTE. Apixaban is effective in both therapeutic and prophylactic doses. Considering both efficacy and bleeding complications, all these agents have a favorable net clinical benefit. Dabigatran is as effective and safe as warfarin for the extended treatment of VTE. It is conceivable that the new oral anticoagulants will become the standard therapy for VTE in the next years.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Humans; Middle Aged; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism; Warfarin

The direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, are new oral anticoagulants that are approved in many countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty. All have a rapid onset of action, a low potential for food and drug interactions and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. These agents offer a convenient alternative to conventional anticoagulant drug regimens, including parenteral low-molecular-weight heparins and fondaparinux, and oral adjusted-dose vitamin K antagonists, for the prevention of venous thromboembolism in this surgical setting. This review summarizes the pharmacology, clinical trial results, bleeding risk and practical use of these new oral anticoagulants in clinical orthopaedic practice. Potential issues to be considered when using these oral anticoagulants include renal impairment, potential drug interactions, neuraxial anaesthesia and management of bleeding.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Heparin, Low-Molecular-Weight; Humans; Morpholines; Postoperative Hemorrhage; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

The risk of venous thrombosis extends for an indeterminate length of time following admission to hospital with a medical or surgical condition. Observational studies in surgery show this risk extends for months and perhaps more than one year, for medical patients the risk extends for at least several weeks. Large bodies of evidence support the heightened risk status of hospitalised surgical and medical patients, and that prophylactic measures significantly reduce the risk of thrombosis. Extending thromboprophylaxis for 4-6 weeks with anticoagulants both old and new has been shown to be efficacious and safe in surgical patients. However in populations of medical patients although prolonged anticoagulant thromboprophylaxis has been shown to be efficacious it also results in more bleeding and the risk benefit is not clear. Hence no therapies are approved for prolonged thromboprophylaxis in medical patients. In this area there have been one phase III study of low molecular weight heparin and two completed phase III studies of NOACs. This article briefly summarises our understanding of the background to preventing venous thromboembolism in hospitalised medical patients and reviews the details of the studies using NOACs.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Enoxaparin; Humans; Morpholines; Postoperative Hemorrhage; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Hemorrhage; Heparin; Humans; Magnetic Resonance Angiography; Morpholines; Pulmonary Artery; Pulmonary Embolism; Rivaroxaban; Thiophenes; Thrombolytic Therapy; Tomography, X-Ray Computed; Venous Thromboembolism

Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs.. The review is based on published phase 3 studies, a literature search in PubMed and the authors' clinical experience.. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment.. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Medication Adherence; Morpholines; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Patients undergoing a total hip or total knee arthroplasty are at high risk of thromboembolism in the postoperative period and after hospital discharge; consequently, clinical guidelines recommended thromboprophylaxis for 10-35 days. Although improved surgical techniques and widespread use of anticoagulants have substantially reduced the incidence of thromboembolic events, venous thromboembolic disease is still a dangerous complication and, in these patients, pulmonary embolism remains the main cause of death. Low molecular weight heparins have long been the mainstay of prevention. However, parenteral administration is inconvenient for many patients, which can sometimes cause poor treatment adherence. In recent years, a new class of oral, fixed-dose anticoagulants, with different mechanisms of action, few interactions and a predictable effect, has been developed. At present, a thrombin inhibitor (dabigatran) and two FXa inhibitors (rivaroxaban and apixaban) are available for prophylaxis in patients after total knee or total hip arthroplasty. In several phase III clinical trials, these drugs have been shown to have equal or superior efficacy and a similar degree of safety to conventional therapy with enoxaparin. These new drugs can significantly improve long-term prevention, particularly in the community setting.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Arterial and venous thrombotic states, including myocardial infarction (MI), stroke and deep vein thrombosis with subsequent pulmonary embolism, are a significant cause of cardiovascular mortality and morbidity. Factor Xa (FXa) plays a pivotal role in thrombus formation. Its inhibition following acute coronary syndromes (ACS) blocks amplification of thrombin generation and subsequent clot formation, resulting in a risk reduction in recurrent MI, stroke and death. For this reason, a predictable form of oral anticoagulation continues to be an ongoing need. Rivaroxaban , the first oral FXa inhibitor, acts by direct inhibition of FXa and does not require an antithrombin cofactor for its activity.. This paper describes the pharmacokinetics (PK) of low-dose rivaroxaban tested in patients with ACS. Age, gender, renal function and body weight have no clinically significant effects on the PK of the drug in treatment of ACS. Caution should be maintained during co-administration of strong CYP3A4 inducers and inhibitors. Among patients with moderate and severe hepatic impairment and in those with associated coagulopathies, rivaroxaban however is contraindicated.. The mortality benefit with low-dose rivaroxaban in ACS patients was first demonstrated in ATLAS ACS2 TIMI-51 trial. With its rapid oral bioavailability, predictable PK, low drug-drug interaction and no need for monitoring, the use of low-dose rivaroxaban in addition to dual antiplatelet therapy offers an appealing new option in improving outcomes following ACS in the modern era of novel oral FXa inhibitors.

Topics: Acute Coronary Syndrome; Administration, Oral; Blood Coagulation Tests; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Evaluation, Preclinical; Drug Interactions; Factor Xa; Factor Xa Inhibitors; Half-Life; Humans; Morpholines; Myocardial Infarction; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Thrombin; Thrombosis

Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists, such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of small molecule factor Xa inhibitors and thrombin inhibitors. With their potentially consistent and predictable clinical profile, oral formulation, and decreased need for coagulation monitoring, these new agents will likely increase the use and duration of anticoagulation treatment in thromboembolic disorders and reduce the burden associated with long-term management.

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Dabigatran; Drug Approval; Humans; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; United States; Venous Thrombosis

Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison.. We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic surgery. We used random effects meta-analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and all-cause mortality), and haemorrhagic adverse events (major and clinically relevant non-major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control.. Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12), and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards increased haemorrhage RR 1.14 (95% CI 0.80-1.64).. Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Heparin; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Morpholines; Neurosurgical Procedures; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stockings, Compression; Surgical Procedures, Operative; Thiophenes; Urologic Surgical Procedures; Venous Thrombosis

The treatment of choice for acute venous thromboembolism is anticoagulant therapy with fast-acting drugs (unfractionated or low-molecular-weight heparin or fondaparinux) aimed at preventing thrombus extension, followed by extended prophylaxis with vitamin K antagonists aimed at preventing recurrence. Experience accumulated over the years has demonstrated that strict laboratory monitoring is required for unfractionated heparin and vitamin K antagonists, making use of these drugs problematic for patients and physicians and prompting researchers to develop new anticoagulants equally effective but without the requirement for laboratory monitoring. The results of clinical trials to date, albeit limited, suggest that these new drugs will probably keep their promise. However, the definitive answer will come subsequent to these clinical trials, when clinicians will start to use these drugs to treat patients in the real world. It is likely that some sort of laboratory monitoring will be required at least for selected categories of patients. Accordingly, clinical laboratories should still be prepared to monitor patients, although the numbers may hopefully decrease sharply in the next decade or so.

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; International Normalized Ratio; Monitoring, Physiologic; Morpholines; Polysaccharides; Prothrombin Time; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The overall thromboembolic risk is the resultant of patient-related risk and surgical risk. The surgical risk is decreasing, especially with the introduction of new procedures (fast-track surgery). The value of prophylaxis has been firmly established. Mechanical prophylaxis is to be used as first-line prophylaxis when there is a risk of bleeding. Combining this with drugs increases the antithrombotic efficacy. However, the effectiveness of prophylaxis on pulmonary embolism and mortality has not been demonstrated. Renal function needs to be evaluated when low molecular weight heparins, fondaparinux, rivaroxaban or dabigatran are prescribed. An age of over 75 years and low body weight (<50 kg) have to be taken into account. There is a risk of spinal or epidural hematoma in patients receiving anticoagulants. Caution should be taken especially when administering the newer agents. Patients undergoing surgery that involves a moderate or high overall risk should receive prophylaxis until full mobilization. Patients who have undergone a total hip replacement, surgery for hip fracture, or major abdominal surgery should receive prophylaxis for about 5 weeks longer. The relevance of distal vein thromboses is debated. Surrogate venographic end-points should be gradually replaced by a combination of ultrasound and clinical criteria. The new antithrombotic agents will probably modify prevention in the years to come but currently there are very few long-term data for these products for which - it should be reminded - no antagonists are available.

Topics: Adult; Aged; Anticoagulants; Combined Modality Therapy; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Morpholines; Polysaccharides; Postoperative Complications; Preanesthetic Medication; Pulmonary Embolism; Risk Factors; Rivaroxaban; Stockings, Compression; Thiophenes; Thromboembolism; Thrombophlebitis; Vitamin K

Anticoagulation for thromboprophylaxis after THA and TKA has not been confirmed to diminish all-cause mortality. We determined whether the incidence of all-cause mortality and pulmonary embolism in patients undergoing total joint arthroplasty differs with currently used thromboprophylaxis protocols. We reviewed articles published from 1998 to 2007 that included 6-week or 3-month incidence of all-cause mortality and symptomatic, nonfatal pulmonary embolism. Twenty studies included reported 15,839 patients receiving low-molecular-weight heparin, ximelagatran, fondaparinux, or rivaroxaban (Group A); 7193 receiving regional anesthesia, pneumatic compression, and aspirin (Group B); and 5006 receiving warfarin (Group C). All-cause mortality was higher in Group A than in Group B (0.41% versus 0.19%) and the incidence of clinical nonfatal pulmonary embolus was higher in Group A than in Group B (0.60% versus 0.35%). The incidences of all-cause mortality and nonfatal pulmonary embolism in Group C were similar to those in Group A (0.4 and 0.52, respectively). Clinical pulmonary embolus occurs despite the use of anticoagulants. Group A anticoagulants were associated with the highest all-cause mortality of the three modalities studied.

Topics: Anesthesia, Conduction; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Azetidines; Benzylamines; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Morpholines; Platelet Aggregation Inhibitors; Polysaccharides; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Treatment Outcome; Warfarin

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N = 722), and one in patients undergoing total knee replacement (TKR; N = 621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5-9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1-24.4% of per-protocol patients receiving rivaroxaban 5-60 mg, and 27.8% receiving enoxaparin (n = 914). There was a flat dose response relationship between rivaroxaban and total VTE (p = 0.39). Major bleeding (safety population, n = 1,317) increased dose-dependently with rivaroxaban (p < 0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5-20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dose-Response Relationship, Drug; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Male; Middle Aged; Morpholines; Phlebography; Pulmonary Embolism; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery.. The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery.. There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups.. Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Topics: Anticoagulants; Chronic Disease; Endarterectomy; Hemorrhage; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

The evaluation and management of patients who sustain recurrent thromboembolic events while taking therapeutic anticoagulation have not been well characterized; moreover, there has been no systematic review or randomized trial focused on treating patients with recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) during anticoagulant treatment. Therefore, we developed a pilot trial to compare rivaroxaban plus aspirin versus acenocoumarol in patients with recurrent venous thromboembolism despite ongoing anticoagulation with rivaroxaban.. The study was a multicenter, randomized clinical trial. We randomly assigned patients with objectively documented recurrent venous thromboembolism to receive rivaroxaban (20 mg once a day) plus aspirin (300 mg once a day) or an adjusted dose of acenocoumarol. The study was designed to evaluate the incidence of recurrent thromboembolic events (recurrent ipsilateral or contralateral DVT, PE, ischemic stroke, and myocardial infarction) and hemorrhagic events.. A total of 58 patients were randomized: 28 were allocated to the rivaroxaban plus aspirin group and 30 to the acenocoumarol group. After 90 days of follow-up, three recurrent thromboembolic events (primary outcome) occurred in the acenocoumarol group - two DVTs and one ischemic stroke - and zero events in the rivaroxaban plus aspirin group (risk ratio [RR] 0.15; 95 % confidence interval [CI] 0.008-2.83; P = 0.20). Minor bleeding occurred in five patients in the acenocoumarol group and zero in the rivaroxaban plus aspirin group (RR 0.09; 95 % CI 0.005-1.68; p = 0.10). There was one non-fatal gastrointestinal major bleed in the rivaroxaban plus aspirin group.. In this pilot study, there were no significant differences in any outcome assessed; however, recurrent thromboembolic events and minor bleeding events occurred numerically less frequently in the rivaroxaban plus aspirin group. These data suggest the need to carry out more extensive randomized studies with sufficient statistical power to clarify these results.

Topics: Acenocoumarol; Anticoagulants; Aspirin; Hemorrhage; Humans; Ischemic Stroke; Pilot Projects; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality after bariatric surgery. Clinical end point studies on thromboprophylaxis with direct oral anticoagulants in patients undergoing bariatric surgery are lacking.. To assess the efficacy and safety of a prophylactic dose of 10 mg/d of rivaroxaban for both 7 and 28 days after bariatric surgery.. This assessor-blinded, phase 2, multicenter randomized clinical trial was conducted from July 1, 2018, through June 30, 2021, with participants from 3 academic and nonacademic hospitals in Switzerland.. Patients were randomized 1 day after bariatric surgery to 10 mg of oral rivaroxaban for either 7 days (short prophylaxis) or 28 days (long prophylaxis).. The primary efficacy outcome was the composite of deep vein thrombosis (symptomatic or asymptomatic) and pulmonary embolism within 28 days after bariatric surgery. Main safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and mortality.. Of 300 patients, 272 (mean [SD] age, 40.0 [12.1] years; 216 women [80.3%]; mean body mass index, 42.2) were randomized; 134 received a 7-day and 135 a 28-day VTE prophylaxis course with rivaroxaban. Only 1 thromboembolic event (0.4%) occurred (asymptomatic thrombosis in a patient undergoing sleeve gastrectomy with extended prophylaxis). Major or clinically relevant nonmajor bleeding events were observed in 5 patients (1.9%): 2 in the short prophylaxis group and 3 in the long prophylaxis group. Clinically nonsignificant bleeding events were observed in 10 patients (3.7%): 3 in the short prophylaxis arm and 7 in the long prophylaxis arm.. In this randomized clinical trial, once-daily VTE prophylaxis with 10 mg of rivaroxaban was effective and safe in the early postoperative phase after bariatric surgery in both the short and long prophylaxis groups.. ClinicalTrials.gov Identifier: NCT03522259.

Topics: Adult; Anticoagulants; Female; Hemorrhage; Humans; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE.. Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE?. In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months.. Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97).. In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided.. ClinicalTrials.gov; No.: NCT02746185; URL: www.. gov.

Topics: Aged; Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla-protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K-dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).. The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two-arm, open-label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre-existent coronary calcification. The development of CVC will be assessed by follow-up CT at 12 and 24 months.. In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Pulmonary Embolism; Rivaroxaban; Stroke; Vitamin K

To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT).. Randomised, double blind, placebo controlled clinical trial.. 28 outpatient clinics specialising in venous thromboembolism.. 402 adults (≥18 years) with symptomatic isolated distal DVT.. After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion.. The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes.. 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred.. Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage.. EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447.

Topics: Adult; Anticoagulants; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis.. This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria.. The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.

Topics: Adult; Brazil; COVID-19; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Thromboembolism; Thrombosis; Venous Thrombosis

Inferior vena cava (IVC) filters are commonly used in patients with venous thromboembolism to prevent fatal pulmonary embolism, but the thrombosis risk increases after filter placement. Warfarin is a widely anticoagulant, but long-term monitoring and dose adjustments are required. Anticoagulation with rivaroxaban is more straightforward as it dose not require laboratory monitoring. This study compares the efficacy and safety of rivaroxaban and warfarin as an in anticoagulation therapy for patients with IVC filter placement.. This is a multicentre, randomised controlled trial. In total, 200 patients with deep vein thrombosis (DVT) with IVC filter implantation from 10 hospitals will be recruited. The patients will be randomised to the experimental group (rivaroxaban) or the control group (nadroparin overlapped with warfarin). The primary outcomes include death of any cause, pulmonary embolism (PE)-related death, bleeding and recurrent PE/DVT. The secondary outcomes include the percentage of other vascular events, IVC filter retrieval failure and net clinical benefits. This study aims to provide reliable, verification for the efficacy and safety of rivaroxaban antithrombotic therapy after IVC filter placement.. The study was approved by the Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval number: (2019) 295). The results will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals TRIAL REGISTRATION NUMBER: NCT04066764.

Topics: Anticoagulants; Contraindications; Humans; Multicenter Studies as Topic; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Vena Cava Filters

It is unknown whether differences in clot structure and resolution contribute to the reported risk differences of recurrent venous thromboembolism (VTE) between men and women.. We used data from the EINSTEIN-PE study, a randomized, multicenter, non-inferiority study in which patients 18 years and older with acute symptomatic pulmonary embolism (PE) were randomized to rivaroxaban or enoxaparin followed by a vitamin K antagonist. PE was diagnosed by computed tomography pulmonary angiography scan or high-probability ventilation/perfusion scintigraphy. Three weeks after randomization a follow-up scan was performed. An independent adjudication committee assessed the degree of vascular obstruction.. A total of 371 participants including 174 (46.9%) women and 197 (53.0%) men were included in the present analysis. At 3 weeks, there was no difference between men and women in complete clot resolution: 39.6% and 40.2%, respectively. The absolute reduction in pulmonary vascular obstruction at week 3 was also similar: 12.9% (95% confidence interval [CI]: 11.6-14.2) in men and 12.1% (95% CI: 10.4-13.7) in women, corresponding to a resolution ratio of 0.29 (95% CI: 0.24-0.33) and 0.35 (95% CI: 0.28-0.42), respectively. No differences in clot resolution were observed between men and women diagnosed with acute PE at 3 weeks after start of anticoagulant therapy. These findings suggest that the reported higher rate of VTE recurrence in men cannot be explained by decreased clot resolution.

Topics: Adolescent; Adult; Anticoagulants; Female; Humans; Male; Pulmonary Embolism; Recurrence; Rivaroxaban; Thrombosis; Venous Thromboembolism

The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial.. This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes.. We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%-1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%-1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%-0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%-9.5%) and was associated with a risk ratio of 6.0 (2.3-15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled.. Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03404635.

Topics: Anticoagulants; Emergency Service, Hospital; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients.. In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding.. A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P<0.001 for noninferiority; P = 0.01 for superiority). The incidence of bleeding did not differ significantly between the rivaroxaban group and the enoxaparin group (1.1% and 1.0%, respectively, for major bleeding or nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding).. Rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilization after nonmajor orthopedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.).

Topics: Administration, Oral; Adult; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Hemorrhage; Humans; Injections, Subcutaneous; Lower Extremity; Male; Middle Aged; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Guidelines suggest using empiric low-molecular-weight heparin if the diagnostic workup of deep vein thrombosis (DVT) is expected to be delayed. The role of direct oral anticoagulants for deferred compression ultrasound imaging (CUS) in patients with suspected DVT remains unexplored. The main objective of the study was to assess the safety of deferring CUS with therapeutic doses of rivaroxaban. We prospectively included consecutive outpatients referred to the Emergency Department at Østfold Hospital, Norway, with suspected first or recurrent lower-extremity DVT between February 2015 and November 2018. Patients were discharged with rivaroxaban 15 mg twice daily while awaiting CUS within 24 hours if D-dimer level was ≥0.5 mg/L fibrinogen-equivalent units. The primary outcome was the rate of major bleeding incidents from study inclusion until DVT was confirmed and anticoagulation therapy continued, or otherwise up to 48 hours following administration of the last tablet of rivaroxaban. The secondary outcome was the rate of progressive DVT symptoms or symptoms or signs of pulmonary embolism between hospital discharge until venous thromboembolism was diagnosed. Six hundred twenty-four of 1653 patients referred with suspected DVT were included (37.7%; 95% confidence interval [CI], 35.4-40.1). DVT was diagnosed in 119 patients (19.1%; 95% CI, 16.1-22.3). There were no major bleeding incidents, yielding an observed major bleeding rate of 0% (1-sided 95% CI <0.4). No patients experienced major complications in the interval that CUS was deferred (0%; 95% CI, 0.0-0.6). Deferring CUS for up to 24 hours in patients with suspected DVT with therapeutic doses of rivaroxaban is a safe strategy. This trial was registered at www.clinicaltrials.gov as #NCT02486445.

Topics: Feasibility Studies; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis

Pancreatic cancer patients are at risk for venous thromboembolism (VTE); the value of thromboprophylaxis has not been definitively established.. This trial randomized cancer patients initiating a new regimen and at high risk for VTE (Khorana score ≥2) to rivaroxaban 10 mg or placebo up to day 180. This analysis examined the subset of pancreatic cancer patients. The primary efficacy endpoint was the composite of symptomatic deep-vein thrombosis (DVT), asymptomatic proximal DVT, any pulmonary embolism, and VTE-related death. The primary safety endpoint was International Society on Thrombosis and Haemostasis-defined major bleeding.. In total, 49/1080 (4.5%) patients enrolled had baseline VTE on screening, with higher rates (24/362 [6.6%]) in pancreatic cancer and they were not randomized. Of 841 randomized patients, 273 (32.5%) had pancreatic cancer; 155/273 (57% in each arm) completed the double-blind period. The primary endpoint occurred in 13/135 (9.6%) patients in the rivaroxaban group and in 18/138 (13.0%) in the placebo group (hazard ratio [HR] = 0.70; 95% CI, 0.34-1.43; P = .328) in up-to-day-180 period and 5/135 (3.7%) patients receiving rivaroxaban and 14/138 (10.1%) receiving placebo in the intervention period (HR = 0.35; 95% CI, 0.13-0.97; P = .034). Major bleeding was similar (2 [1.5%] receiving rivaroxaban and 3 [2.3%] receiving placebo). Correlative biomarker studies demonstrated significant decline in D-dimer (weeks 8 and 16) in patients randomized to rivaroxaban compared to placebo (P < .01).. In ambulatory pancreatic cancer patients, rivaroxaban did not result in significantly lower incidence of VTE or VTE-related death in the 180-day period. During the intervention period, however, rivaroxaban substantially reduced VTE without increasing major bleeding, suggesting benefit of rivaroxaban prophylaxis in this setting.. ClinicalTrials.gov identifier, NCT02555878.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Incidence; Male; Middle Aged; Outpatients; Pancreatic Neoplasms; Placebos; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Pulmonary embolism (PE) is a life-threatening disease. Target-specific anticoagulant rivaroxaban is a direct factor Xa inhibitor that can be safely used without laboratory monitoring.. To investigate the efficacy and safety of rivaroxaban versus warfarin for the treatment of acute pulmonary thromboembolism in real-world clinical practice.. This was a semiretrospective, semiprospective, and real-world trial involving 128 patients with acute symptomatic pulmonary embolism with or without active tumor or frailty. We compared rivaroxaban to the standard therapy consisting of low-molecular-weight heparin combined with warfarin. The primary efficacy outcome was absorption of thrombus. The principal safety outcome was bleeding episode.. There was no significant difference in thrombus absorption between rivaroxaban and standard therapy after 3-month treatment (. In this real-world study, the efficacy and safety of rivaroxaban alone was not different to standard therapy for pulmonary emboli absorption. With an extension in treatment duration, the rivaroxaban regimen had a higher efficacy and safety than standard therapy and there was no decline in treatment efficacy when the rivaroxaban dose was reduced to 10 mg once daily.

Topics: Female; Frailty; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Risk Factors; Rivaroxaban; Treatment Outcome; Warfarin

To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban.. We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%).. Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Outpatients; Patient Discharge; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Treatment Outcome; Young Adult

Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients.. In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/ metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication.. Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died.. Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Blood Coagulation; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Neoplasms; Prospective Studies; Pulmonary Embolism; Recurrence; Republic of Korea; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Direct oral anticoagulants (DOACs) are frequently used for the treatment of pulmonary embolism (PE), but both clinical and laboratory data comparing their efficacy and safety are conflicting. This study investigated and compared the impact of three DOACs (apixaban, rivaroxaban and dabigatran) on coagulation cascade in acute PE patients.. After the initial treatment, acute PE patients were randomly allocated to one of three groups, and treatment continued using one of the three DOACs. Following 1 month of treatment, the activity of factors II, VII and VIII, as well as protein C, antithrombin, D-dimer and fibrinogen, were measured, and the values were compared between the groups.. One hundred consecutive PE patients were included. The mean values for the activity of factors II and VII and protein C were higher in patients on apixaban than in patients on rivaroxaban (1.45 ± 1.12 (IU/mL) vs 1.13 ± 0.92 (IU/mL), P < 0.001; 1.24 ± 1.10 (IU/mL) vs 1.05 ± 0.98 (IU/mL), P = 0.024 and 1.15 ± 0.62 vs 1.02 ± 0.68 (IU/mL), P = 0.019, respectively). The mean of factor II activity and the median of factor VIII activity were also significantly higher in patients on apixaban than in patients on dabigatran (1.45 ± 1.12 vs 1.20 ± 0.96 (IU/mL), P = 0.003 and 2.9 (2.0-4.0) vs 2.1 (1.5-2.7) (IU/mL), P = 0.001, respectively). No difference was noticed in D-dimer concentrations, or in the activity of the other factors measured. Additionally, no difference was noticed between the rivaroxaban and dabigatran groups.. Apixaban had a significantly higher thrombin activity, above the laboratory determined normal range, compared to patients on rivaroxaban and dabigatran. This higher thrombin activity in patients on apixaban may contribute to a better haemostatic response during the therapy or increased prothrombotic state after therapy interruption.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Anticoagulants; Blood Coagulation Factors; Dabigatran; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thrombin; Treatment Outcome

Whether anticoagulation benefits patients with heart failure (HF) in sinus rhythm is uncertain. The COMMANDER HF randomized clinical trial evaluated the effects of adding low-dose rivaroxaban to antiplatelet therapy in patients with recent worsening of chronic HF with reduced ejection fraction, coronary artery disease (CAD), and sinus rhythm. Although the primary end point of all-cause mortality, myocardial infarction, or stroke did not differ between rivaroxaban and placebo, there were numerical advantages favoring rivaroxaban for myocardial infarction and stroke.. To examine whether low-dose rivaroxaban was associated with reduced thromboembolic events in patients enrolled in the COMMANDER HF trial.. Post hoc analysis of the COMMANDER HF multicenter, randomized, double-blind, placebo-controlled trial in patients with CAD and worsening HF. The trial randomized 5022 patients postdischarge from a hospital or outpatient clinic after treatment for worsening HF between September 2013 and October 2017. Patients were required to be receiving standard care for HF and CAD and were excluded for a medical condition requiring anticoagulation or a bleeding history. Patients were randomized in a 1:1 ratio. Analysis was conducted from June 2018 and January 2019.. Patients were randomly assigned to receive 2.5 mg of rivaroxaban given orally twice daily or placebo in addition to their standard therapy.. For this post hoc analysis, a thromboembolic composite was defined as either (1) myocardial infarction, ischemic stroke, sudden/unwitnessed death, symptomatic pulmonary embolism, or symptomatic deep venous thrombosis or (2) all of the previous components except sudden/unwitnessed deaths because not all of these are caused by thromboembolic events.. Of 5022 patients, 3872 (77.1%) were men, and the overall mean (SD) age was 66.4 (10.2) years. Over a median (interquartile range) follow-up of 19.6 (11.7-30.8) months, fewer patients assigned to rivaroxaban compared with placebo had a thromboembolic event including sudden/unwitnessed deaths: 328 (13.1%) vs 390 (15.5%) (hazard ratio, 0.83; 95% CI, 0.72-0.96; P = .01). When sudden/unwitnessed deaths were excluded, the results analyzing thromboembolic events were similar: 153 (6.1%) vs 190 patients (7.6%) with an event (hazard ratio, 0.80; 95% CI, 0.64-0.98; P = .04).. In this study, thromboembolic events occurred frequently in patients with HF, CAD, and sinus rhythm. Rivaroxaban may reduce the risk of thromboembolic events in this population, but these events are not the major cause of morbidity and mortality in patients with recent worsening of HF for which rivaroxaban had no effect. While consistent with other studies, these results require confirmation in prospective randomized clinical trials.. ClinicalTrials.gov identifier: NCT01877915.

Topics: Aged; Aspirin; Chronic Disease; Coronary Artery Disease; Death, Sudden; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Heart Failure; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pulmonary Embolism; Rivaroxaban; Stroke; Stroke Volume; Thienopyridines; Thromboembolism; Venous Thrombosis

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Topics: Aged; Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Propensity Score; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Survival Analysis; Treatment Outcome; Venous Thromboembolism

Little data exist on the use of direct oral anticoagulant (DOAC) factor Xa inhibitors for submassive pulmonary embolism (PE) after catheter-directed thrombolysis (CDT). The objective of this evaluation was to determine whether the transition from parenteral anticoagulation to DOACs for submassive PE after CDT would decrease hospital length of stay (LOS) compared to warfarin.. A retrospective review of patients diagnosed with submassive PE who underwent CDT was conducted from January 1, 2012, to February 28, 2017. Hospital LOS and major and minor bleeding events were recorded during hospitalization and at 90 days.. Sixty-two patients met the inclusion criteria, 36 in warfarin group and 26 in the DOAC group. Overall, patients receiving rivaroxaban or apixaban had a shorter median hospital LOS compared to warfarin (4.0 vs 6.1 days, P = .002). In the multivariate regression analysis, administration of DOAC was an independent predictor of decreased hospital LOS, β: -2.1, 95% confidence interval (-3.5 to -0.7).. Among patients with submassive PE, initiation of a DOAC shortly after CDT may result in a decreased hospital LOS compared to parenterally bridged warfarin.

Topics: Aged; Female; Humans; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thrombolytic Therapy; Warfarin

Hospitalization for low-risk pulmonary embolism (PE) is common, expensive, and of questionable benefit.. The objective was to determine if low-risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC).. Multicenter, open-label randomized trial in low-risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90-day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality.. Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of -28.8 hours (95% confidence interval [CI] = -42.55 to -15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = -46.97 to -3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = -0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = -$2,999 to -$2,151).. Low-risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days.

Topics: Adult; Aged; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Humans; Length of Stay; Male; Middle Aged; Outcome Assessment, Health Care; Patient Discharge; Pulmonary Embolism; Rivaroxaban; Standard of Care; Young Adult

The effectiveness of preoperative thromboprophylaxis remains obscure in patients with femoral neck fracture. The purpose of the current study was to investigate whether these patients benefit from preoperative thromboprophylaxis.. In this prospective, randomized controlled trial, a total of 80 patients with femoral neck fracture were randomly assigned to receive either rivaroxaban or conservative treatment before surgery. For all patients, color Doppler ultrasound of both lower extremities was performed immediately after admission. The primary efficacy outcome was venous thromboembolism (VTE) defined as deep vein thrombosis (DVT) or pulmonary embolism (PE). The primary safety outcome was major bleeding.. Compared with conservative treatment, rivaroxaban could significantly reduce the incidence of DVT from 19.5% (8/41) to 2.6% (1/39) (P = .016). Preoperatively, there were a total of 9 occurrences of DVT including 8 DVT in the conservative treatment group and 1 in the oral rivaroxaban group. All cases of DVT were asymptomatic, with 8 of them diagnosed as isolated muscular calf vein thromboses. There were no differences between the 2 groups in terms of the overall incidence of major bleeding.. Thromboprophylaxis with rivaroxaban prior to surgery can effectively reduce the risk of preoperative DVT for patients with femoral neck fracture without increasing the risk of bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Conservative Treatment; Factor Xa Inhibitors; Female; Femoral Neck Fractures; Hemorrhage; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Preoperative Care; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis

Venous thromboembolism (VTE) is a frequent complication of cancer associated with morbidity, mortality, increased hospitalizations and higher health care costs. Cancer patients at increased risk for VTE can be identified using a validated risk assessment score, and the incidence of VTE can be reduced in high-risk settings using anticoagulation. Rivaroxaban is a potent, oral, direct, factor Xa inhibitor approved for the prevention and treatment of thromboembolic events, including VTE. CASSINI is a double-blind, randomized, parallel-group, multicentre study comparing rivaroxaban with placebo in adult ambulatory patients with various cancers who are initiating systemic cancer therapy and are at high risk of VTE (Khorana score ≥ 2). Patients with primary brain tumours or those at risk for bleeding are excluded. Approximately 700 patients will be randomized 1:1 to rivaroxaban 10 mg daily or placebo for up to 6 months if there is no evidence of VTE from compression ultrasonography (CU) during screening or from routine care imaging within 30 days prior to randomization. Mandatory CU will also be performed at weeks 8 and 16 (±7 days), and at study end (±3 days). The primary efficacy hypothesis is that anticoagulation with rivaroxaban reduces the composite of objectively confirmed symptomatic or asymptomatic, lower-extremity, proximal deep-vein thrombosis (DVT); symptomatic, upper-extremity DVT; symptomatic or incidental pulmonary embolism; and VTE-related death compared with placebo. The primary safety objective is to assess major bleeding events (Clinical trial information: NCT02555878).

Topics: Ambulatory Care; Blood Coagulation; Clinical Protocols; Double-Blind Method; Europe; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Neoplasms; North America; Pulmonary Embolism; Research Design; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Topics: Adult; Anticoagulants; Brain Injuries, Traumatic; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thrombosis

Tranexamic acid (TXA) was reportedly to decrease postoperative blood loss after standard total knee arthroplasty (TKA). However, the blood-conservation effect of TXA in minimally invasive TKA, in particular, receiving a direct oral anticoagulant was unclear. The aim of the study was to investigate the efficacy of combined use of TXA and rivaroxaban on postoperative blood loss in primary minimally invasive TKA.. In a prospective, randomized, controlled trial, 198 patients were assigned to placebo (98 patients, normal saline injection) and study group (100 patients, 1g TXA intraoperative injection) during primary unilateral minimally invasive TKA. All patients received rivaroxaban 10 mg each day for 14 doses postoperatively. Total blood loss was calculated from the maximum hemoglobin drop after surgery plus amount of transfusion. The transfusion rate and wound complications were recorded in all patients. Deep-vein thrombosis was detected by ascending venography of the leg 15 days postoperatively.. The mean total blood loss was lower in the study group (1020 mL [95% confidence interval, 960-1080 mL]) compared with placebo (1202 mL [95% confidence interval, 1137-1268 mL]) (P < .001). The transfusion rate was lower in the study group compared with placebo (1% vs 8.2%, P = .018). Postoperative wound hematoma and ecchymosis were higher in placebo than the study group (P = .003). There was no symptomatic deep-vein thrombosis or pulmonary embolism in either group.. Systemic administration of TXA can effectively reduce the postoperative blood loss which results in lower rate of transfusion requirement and wound hematoma in minimally invasive TKA patients when rivaroxaban is used for thromboprophylaxis. Rivaroxaban has a high rate of bleeding complications when used alone in TKA patients.

Topics: Aged; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hematoma; Humans; Male; Middle Aged; Morpholines; Postoperative Hemorrhage; Postoperative Period; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Thiophenes; Tranexamic Acid; Venous Thrombosis

Multiple randomized controlled trials have documented the effectiveness of rivaroxaban in the prevention of venous thromboembolism up to 1-month following total joint arthroplasty. However, the effectiveness and safety of rivaroxaban in the real-world setting, outside of the strict protocols used by randomized clinical trials, are unknown.. This was a prospective, observational, noninterventional, phase IV study of 3914 consecutive patients who underwent total joint arthroplasty from June 2010 to December 2012. Patients were treated with rivaroxaban 10 mg by mouth daily starting postoperative day 1 and continued for 15 days. Participants were followed up in clinic at 6 weeks and contacted by telephone at 12 weeks. The primary outcome of interest was symptomatic venous thromboembolism; secondary outcomes included bleeding events, transfusion requirements, and death.. The incidence of symptomatic deep venous thrombosis at 3 months was 0.5% (n = 18). Only 1 deep venous thrombosis event occurred within 7 days of surgery. The incidence of symptomatic pulmonary embolism (PE) at 3 months was 0.7% (n = 28). Thirteen PEs (46%) occurred within 7 days of surgery. The rate of major bleeding while on prophylaxis was 0.1%. Only 5% of patients received a blood transfusion. No deaths were attributed to thromboembolic events.. This prospective, observational, phase IV study demonstrates that rivaroxaban appears to protect patients against symptomatic PE and is not associated with major bleeding events when used in a real-world setting as described.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Young Adult

Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure.. GALILEO is an international, randomized, open-label, event-driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days after a successful TAVR, to either a rivaroxaban-based strategy or an antiplatelet-based strategy. In the experimental arm, subjects receive rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD) for 90days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In case new-onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all-cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life-threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions.. GALILEO will test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the risk of thromboembolic complications post-TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy-based strategy in subjects without need of chronic oral anticoagulation.

Topics: Aortic Valve Stenosis; Aspirin; Cardiovascular Diseases; Cause of Death; Clopidogrel; Drug Therapy, Combination; Embolism; Factor Xa Inhibitors; Heart Valve Diseases; Humans; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Care; Pulmonary Embolism; Rivaroxaban; Stroke; Thrombosis; Ticlopidine; Transcatheter Aortic Valve Replacement; Venous Thrombosis

BACKGROUND This study aimed to assess whether the efficacy of tranexamic acid (TXA) would be altered when rivaroxaban or enoxaparin was used for thromboprophylaxis in primary total knee replacement (TKR). It was hypothesized that the hemostatic effect of TXA would be better with the use of enoxaparin. MATERIAL AND METHODS A randomized clinical trial was conducted on 194 patients undergoing primary TKR for osteoarthritis. An intravenous dose of 15 mg/kg (TXA) and 1 g topical TXA were used. Patients randomly received enoxaparin or rivaroxaban prophylaxis when the drainage was less than 30 ml/h 6-8 h postoperatively. The primary endpoint was hidden blood loss (HBL). Indexes of total blood loss drainage, hemoglobin drop, transfusion, range of motion (ROM), HSS score, VAS pain score, knee swelling, length of hospital stay (LOHS), incidence of venous thromboembolism, major/minor bleeding, and wound complications were also compared between the groups. RESULTS More than 80% of patients initiated anticoagulation within 6 h postoperatively. No statistically significance difference was detected in terms of HBL (679.0±205.6 vs. 770.5±206.1, p=.062) or other bleeding index, ROM, or LOHS. The motion VAS pain score and knee swelling (16.7% vs. 6.1%, p=.021) were significantly lower, and HSS score at discharge was higher in the enoxaparin group. The rivaroxaban group had less asymptomatic deep venous (4.1% vs. 0%, p=.121) and muscular venous thrombosis (2.1% vs. 9.2%, p=.033); more ecchymosis (13.5% vs. 10.2%, p=.472), and wound complications (13.5% vs. 6.1%, p=.082). No episodes of transfusion, pulmonary embolism, or major bleeding occurred in either group. CONCLUSIONS More attention should be paid to the increased risk of wound complications and knee swelling associated with rivaroxaban, although the hidden blood loss was similar in both groups.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Coagulation; Drug Interactions; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Osteoarthritis; Pilot Projects; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Tranexamic Acid; Venous Thromboembolism

Superficial-vein thrombosis can lead to deep-vein thrombosis and pulmonary embolism. Rivaroxaban, an oral factor Xa inhibitor, might simplify treatment compared with fondaparinux because it does not require daily subcutaneous injection and is cheaper. We compared efficacy outcomes in patients with superficial-vein thrombosis and additional risk factors given either rivaroxaban or fondaparinux to assess whether rivaroxaban is non-inferior to fondaparinux in the prevention of thromboembolic complications.. In this open-label, masked endpoint, randomised, non-inferiority phase 3b trial, we recruited patients aged 18 years or older with symptomatic superficial-vein thrombosis from 27 sites (academic, community hospitals, and specialist practices) in Germany. We randomly assigned patients (1:1) to receive 10 mg oral rivaroxaban or 2·5 mg subcutaneous fondaparinux once a day for 45 days. Patients were eligible if they had symptomatic thrombosis (at least 5 cm in a supragenual superficial-vein segment) and at least one additional risk factor (older than 65 years, male sex, previous venous thromboembolism, cancer, autoimmune disease, thrombosis of non-varicose veins). Main exclusion criteria were: symptoms for longer than 3 weeks, thrombus within 3 cm of the sapheno-femoral junction, indication for full-dose anticoagulation therapy, and substantial hepatic or renal impairment. Randomisation was done with a central block randomisation process. The primary efficacy outcome was a composite of symptomatic deep-vein thrombosis or pulmonary embolism, progression or recurrence of superficial vein-thrombosis, and all-cause mortality at 45 days in the per-protocol population (all randomly assigned patients without major protocol violations). We used a non-inferiority margin of 4·5% (absolute difference between rivaroxaban and fondaparinux). The main safety outcome was major bleeding. This study is registered with ClinicalTrials.gov, number NCT01499953.. Between April 25, 2012, and Feb 18, 2016, 485 patients were enrolled in the study and 472 were randomly assigned to the rivaroxaban group (n=236) or the fondaparinux group (n=236). In the 435 patients included in the per-protocol analysis set, the primary efficacy outcome occurred in seven (3%) of 211 patients (95% CI 1·6-6·7) in the rivaroxaban group and in four (2%) of 224 patients (0·7-4·5) in the fondaparinux group (hazard ratio [HR] 1·9, 95% CI 0·6-6·4; p=0·0025 for non-inferiority) at day 45. There were no major bleeds in either group. There was one death in the rivaroxaban group; this patient died from cardiogenic shock on day 50 after a type A aortic dissection, not related to treatment.. Rivaroxaban was non-inferior to fondaparinux for treatment of superficial-vein thrombosis in terms of symptomatic deep-vein thrombosis or pulmonary embolism, progression or recurrence of superficial vein-thrombosis, and all-cause mortality, and was not associated with more major bleeding. Therefore, rivaroxaban could offer patients with symptomatic superficial-vein thrombosis a less burdensome and less expensive oral treatment option instead of a more expensive subcutaneous injection.. GWT-TUD and Bayer Vital.

Topics: Aged; Aged, 80 and over; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Rivaroxaban; Thrombosis; Venous Thrombosis

Acute venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is traditionally managed with a short course of parenteral anticoagulation followed by 3-6 months of a vitamin-K antagonist. Non-vitamin K oral anticoagulants (NOACs) do not require routine monitoring and dose adjustment, thus potentially provide an alternative treatment option.. Because of the lack of head-to-head clinical studies, an indirect comparison was conducted of dabigatran etexilate and rivaroxaban based on the respective phase III clinical trial. The derived relative safety and efficacy estimates were used to evaluate the cost-utility of dabigatran compared with rivaroxaban in the treatment and secondary prevention of VTE. The results of the indirect comparison showed no significant difference between dabigatran and rivaroxaban in avoiding recurrent VTE following index PE, index DVT, or DVT/PE combined, in treatment and extended anticoagulation. Dabigatran has significantly less major or clinically relevant bleeds (MCRBE) compared to rivaroxaban in treatment after index DVT and treatment after DVT or PE combined, but was not significantly different from rivaroxaban after index PE or in extended anticoagulation. In cost-utility deterministic analyses, dabigatran was projected dominant in all analyzed settings, given its marginally lower total cost and marginally higher QALYs gained compared to rivaroxaban. Probabilistic analyses results showed a high likelihood of dabigatran being considered good value for money in the UK, in treatment and in secondary prevention of VTE.. The cost-effectiveness evaluations showed that dabigatran can be considered the dominant treatment strategy compared to rivaroxaban in the patients' sub-groups considered, given the projected marginally higher clinical benefits and lower treatment costs.

Topics: Anticoagulants; Cost-Benefit Analysis; Dabigatran; Double-Blind Method; Female; Health Services; Hemorrhage; Humans; Male; Middle Aged; Models, Econometric; Pulmonary Embolism; Quality-Adjusted Life Years; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE.

Topics: Administration, Oral; Factor Xa Inhibitors; Home Care Services; Humans; Patient Discharge; Prospective Studies; Pulmonary Embolism; Quality of Life; Recurrence; Risk Factors; Rivaroxaban; Self Administration

Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism. Rivaroxaban is an oral anticoagulant, which directly inhibits Factor Xa. The objective of the current study was, in comparison to the standard-therapy method, to investigate the potential of rivaroxaban to improve the treatment of patients with PE, and to reduce hemorrhage in the standard-therapy group through adjusting the dose of warfarin by CYP2C9 and VKORC1 genotypes.. Sixty-two PE patients with or without deep venous thrombosis (DVT) was randomized to rivaroxaban mono-therapy or standard-therapy with enoxaparin followed by vitamin K antagonist (VKA). Concentration of the anticoagulants was adjusted according to the results of CYP2C9 and VKORC1 genotypes in order to stabilize the international normalized rate (INR) at 2.0-3.0 range. Length of hospital stay at initial hospitalization was compared, therapeutic efficacy was examined by computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion (V/Q) scan, and side-effect of anti-coagulants was monitored at 1-month, and 3- or 6-months follow-up check points.. We found that, overall, patients who received rivaroxaban mono-therapy had a significantly shorter length of hospital stay compared with patients who received standard-therapy of enoxaparin followed by VKA (9.29±3.70 versus 11.38±3.12days, P=0.021). The therapeutic efficacy was of no marked difference between these two groups. However, after one month treatment, 50% (16/32) of the standard-therapy group had mild hemorrhage, which was significantly higher than that of rivaroxaban mono-therapy group (16.7%, 5/30, P=0.006). Moreover, a significantly higher rate in the standard-therapy group (22.2% versus 3.4%, P=0.032) was found after 3 or 6months therapy. Major bleeding was slightly but not significantly higher in the standard-therapy group than that in the rivaroxaban therapy group. In addition, 2 (6.3%) patients died from Life-threatening bleeding in the standard-therapy group.. Findings of the current study suggested that rivaroxaban mono-therapy result in shorter hospital stay compared to the standard-therapy. Implication of CYP2C9 and VKORC1 genotypes in determining dose of warfarin, however, remains to be further examined in larger cohort studies.

Topics: Administration, Oral; Anticoagulants; Cytochrome P-450 CYP2C9; Enoxaparin; Genotype; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Short-term anticoagulant treatment for acute DVT or pulmonary embolism (PE) effectively reduces the risk of recurrent disease during the first 6 to 12 months of therapy. Continued anticoagulation often is not instituted because of the perception among physicians that the risk of major bleeding will outweigh the risk of new venous thrombotic episodes.. The authors performed a benefit-risk analysis by using the randomized EINSTEIN-Extension trial, which compared continued rivaroxaban with placebo in 1,197 patients with symptomatic DVT or PE who had completed 6 to 12 months of anticoagulation and in whom physicians had equipoise with respect to the need for continued anticoagulation. One-year Kaplan-Meier rates and rate differences of recurrent VTE and major bleeding were calculated. Benefits and risks were assessed using rate differences scaled to a population size of 10,000 patients treated for 1 year.. Recurrent VTE occurred in eight recipients of rivaroxaban and 42 patients receiving placebo. In a population of 10,000 patients treated for 1 year, rivaroxaban treatment would have resulted in 665 (95% CI, 246-1,084) fewer recurrent VTEs than would placebo (number needed to treat = 15). Major bleeding occurred in four (0.7%) and zero patients, respectively. Rivaroxaban treatment would have resulted in 68 (95% CI, 2-134) more major bleeding events than would placebo (number needed to harm = 147). Kaplan-Meier analysis showed early recurrent VTE reduction with rivaroxaban that continued to improve throughout treatment; major bleeding increased gradually, plateauing at approximately 100 days.. A clinically important benefit and a favorable benefit-risk profile of continued rivaroxaban anticoagulation was observed.. ClinicalTrials.gov; No.: NCT00439725; URL: www.clinicaltrials.gov.

Topics: Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Survival Rate; Treatment Outcome; Venous Thromboembolism

Traditionally, patients with pulmonary embolism (PE) are admitted from the emergency department and treated with low-molecular-weight heparin followed by warfarin. Several studies now demonstrate that it is possible to identify low-risk PE patients that can safely be treated as outpatients. The advent of the direct-acting oral anticoagulants such as rivaroxaban has made it easier than ever to manage patients outside of the hospital. This article describes the design of a randomized controlled trial aimed at testing the hypothesis that low-risk PE patients can be safely and effectively managed at home using rivaroxaban, resulting in fewer days of hospitalization than standard-of-care treatment.. We have initiated a multicenter, open-label, randomized clinical trial in which low-risk adult PE patients (identified by the Hestia criteria) are randomized to outpatient management with oral rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily for 90 days versus standard care, determined by the treating physician and based on local practices. The primary clinical endpoint will be the total number of inpatient hospital days (including the index admission) for venous thromboembolic or bleeding-related events during the first 30 days after randomization. A total of 150 subjects per group will provide 82% power to detect a difference of 1 day or greater in the primary outcome.. Patient enrollment is ongoing at present in 45 of 60 planned sites. No interim analysis is planned and the study is being monitored by a data safety management board.. The MERCURY PE study is designed to test the hypothesis that outpatient management of low-risk PE patients with rivaroxaban reduces the number of hospitalization days from venous thromboembolism and bleeding compared with standard care. This article describes the rationale and methodology for this study.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Hospitalization; Humans; Pulmonary Embolism; Research Design; Rivaroxaban; Venous Thromboembolism

Rivaroxaban is an oral, direct Factor Xa inhibitor, approved for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT) and the secondary prevention of recurrent PE and DVT as a fixed-dose, monotherapy regimen that does not require initial heparinisation, routine coagulation monitoring or dose adjustment. Approval in this indication was supported by results from EINSTEIN PE, a large, randomised, open-label study that compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy in patients with acute symptomatic PE with or without DVT.. Patient-reported treatment satisfaction was evaluated in a predefined subanalysis of EINSTEIN PE to enable monitoring and optimisation of patient-reported outcomes and, therefore, patient compliance. As part of EINSTEIN PE, 2,397 patients in seven countries were asked to complete a validated measure of treatment satisfaction, the Anti-Clot Treatment Scale (ACTS) throughout the duration of treatment (up to 12 months).. Patients reported greater satisfaction in the rivaroxaban treatment arm as compared with the enoxaparin/VKA treatment arm. Treatment with rivaroxaban was reported as being significantly less burdensome than enoxaparin/VKA therapy, and the benefits of treatment were significantly greater.. Rivaroxaban treatment resulted in improved treatment satisfaction compared with enoxaparin/VKA in PE patients, particularly in reducing patient-reported anticoagulation burden.

Topics: Administration, Oral; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Patient Satisfaction; Pulmonary Embolism; Rivaroxaban; Thiophenes

The objective was to assess adverse outcomes in relation to the simplified Pulmonary Embolism Severity Index (PESI) score in patients treated with rivaroxaban or standard therapy in the phase III EINSTEIN PE study and to evaluate the utility of the simplified PESI score to identify low-risk pulmonary embolism (PE) patients.. A post hoc analysis of EINSTEIN PE data was performed to assess the efficacy and safety of rivaroxaban in patients with a range of simplified PESI scores. Recurrent venous thromboembolism, fatal PE, all-cause mortality, and major bleeding were stratified by simplified PESI scores of 0, 1, or ≥2 and according to treatment period at 7, 14, 30, and 90 days and at the end of the full intended treatment period.. Simplified PESI scores could be calculated in 4,831 of the 4,832 randomized patients; of those, 53.6, 36.7, and 9.7% had PESI scores of 0, 1, and ≥2, respectively. Among patients with simplified PESI scores of 0 or 1, fatal PE, all-cause mortality, and other adverse outcomes were uncommon within the first 7, 14, and 30 days. Patients with simplified PESI scores of ≥2 had more frequent adverse outcomes. Major bleeding was lower in the rivaroxaban group, particularly in those with simplified PESI scores of 1 or ≥2.. The findings support using risk stratification with the simplified PESI score to identify low-risk patients with PE.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Comorbidity; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Predictive Value of Tests; Prognosis; Pulmonary Embolism; Risk; Rivaroxaban; Severity of Illness Index; Thiophenes

Compared to warfarin, the non-vitamin K antagonist oral anticoagulant rivaroxaban may have advantages in treating patients with venous thromboembolism, because injectable bridging therapy and routine laboratory monitoring are not required. The objective of this study was to compare the rate of hospitalization in patients treated with rivaroxaban after its introduction with what it would have been before the introduction of rivaroxaban.. A retrospective claims analysis was conducted using the MarketScan Hospital Drug Database from January 2011 to December 2013. Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) bridged to warfarin during the first day of an evaluation at a hospital were identified. Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients, and the rates of hospitalization were compared.. All rivaroxaban-treated patients (n = 134) in the database were well matched with four historical LMWH/warfarin-treated patients (n = 536). Among the rivaroxaban cohort, 60% of the patients were admitted to the hospital, compared to 82% of the historical patients treated with LMWH/warfarin in the matched cohort. The difference was statistically significant and corresponded to a 27% reduction in hospital admissions (rate ratio [95% confidence interval]: 0.73 [0.62-0.84]). Hospital admission rates adjusted for time-trend analyses also led to similar results.. The availability of rivaroxaban significantly reduced the hospitalization rate in patients with DVT treated with rivaroxaban compared to what it would have been if only LMWH/warfarin were available.

Topics: Adult; Anticoagulants; Cohort Studies; Female; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis

In Japan, the standard of care for the treatment of pulmonary embolism (PE) and/or deep vein thrombosis (DVT) consists of intravenous unfractionated heparin (UFH) followed by warfarin, which was recently compared with rivaroxaban, an oral factor Xa inhibitor, in randomized trials.. To examine the length of hospital stay in patients with PE and/or DVT receiving rivaroxaban compared to Japanese standard therapy in the Japanese (J)-EINSTEIN PE and DVT program.. Open-label, randomized clinical trials that compared 3, 6, or 12 months of rivaroxaban with UFH and warfarin in patients with acute, confirmed symptomatic proximal PE and/or DVT. Decisions regarding hospital admission and/or discharge were left to the clinical judgment of attending physicians. Analyses were conducted in the intention-to-treat (ITT) population.. In the ITT population (N = 97), overall patient characteristics were similar in both treatment arms. The median length of stay in rivaroxaban patients was 10.0 days (interquartile range [IQR] 6.0 to 15.0 days) while it was 15.0 days (IQR 9.0 to 22.0) for patients on standard therapy (p = 0.016). All of the four DVT patients who were not hospitalized for the index event were in the rivaroxaban arm.. Our results suggest that treatment with rivaroxaban may significantly reduce the length of hospital stay in patients hospitalized for PE and/or DVT compared with the current standard of care in Japan, thereby reducing the burden on patients and the healthcare system. The limitations of our study include small sample size and the generalizability of the findings to the real-world setting. Further research is warranted to identify PE and/or DVT patients in Japanese clinical practice who may potentially be managed as outpatients.. Clinicaltrials.gov: NCT01516814 and NCT01516840.

Topics: Aged; Aged, 80 and over; Anticoagulants; Asian People; Female; Heparin; Humans; Japan; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

Rivaroxaban is a new oral anticoagulant (NOAC) that can be prescribed in a fixed dose, making regular monitoring and dose adjustments unnecessary. It has been proven to be safe and effective in comparison with enoxaparin/vitamin K antagonists (LMWH/VKA) for the (extended) treatment of venous thromboembolism in the EINSTEIN studies. Nevertheless, there is a need for information regarding the clinical impact of (major) bleeding events with NOACs such as rivaroxaban.. A post-hoc analysis was performed to compare the severity of clinical presentation and subsequent clinical course of major bleeding with rivaroxaban vs. LMWH/VKA.. Two investigators performed a blinded classification of major bleeding using a priori defined criteria. During the EINSTEIN studies, data concerning the clinical course and measures applied were prospectively collected for each major bleed.. Treatment with LMWH/VKA caused more major bleeding events (1.7%) than rivaroxaban (1.0%; hazard ratio, 0.54; 95% confidence interval [CI], 0.37-0.79). Major bleeding events during rivaroxaban therapy had a milder presentation (23% were adjudicated to the worst categories vs. 38% for LMWH/VKA; hazard ratio or HR, 0.35; 95% CI, 0.17-0.74; P = 0.0062). The clinical course was severe in 25% of all major bleeding events associated with rivaroxaban, compared with 33% of LMWH/VKA-associated bleeds (HR, 0.46; 95% CI, 0.22-0.96; P = 0.040).. Rivaroxaban-associated major bleeding events occurred less frequently, had a milder presentation and appeared to take a less severe clinical course compared with major bleeding with LMWH/VKA.

Topics: Anticoagulants; Blood Coagulation Factors; Factor VIIa; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Kaplan-Meier Estimate; Plasma; Prospective Studies; Pulmonary Embolism; Recombinant Proteins; Rivaroxaban; Severity of Illness Index; Single-Blind Method; Thrombophilia; Venous Thrombosis; Vitamin K

The phase III EINSTEIN DVT and EINSTEIN PE trials demonstrated the potential of oral rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). The length of initial hospitalization in patients presenting with either symptomatic DVT or PE was assessed using hospitalization records from these trials.. Analyses were carried out in the intention-to-treat population, using non-parametric and parametric statistical methods.. Overall, 52% (1781/3434) of EINSTEIN DVT patients and 90% (4328/4821) of EINSTEIN PE patients were admitted to hospital. The proportion of hospitalized patients with a length of stay of five or fewer days receiving rivaroxaban was 54% compared with 31% for enoxaparin/vitamin K antagonist (VKA) in patients with DVT. For patients with PE, the corresponding values were 45% and 33%. Stays of 6-10 days were observed in 29% of rivaroxaban-treated patients compared with 45% of enoxaparin/VKA-treated patients for DVT. For patients with PE, these values were 39% and 46% in the rivaroxaban and enoxaparin/VKA groups, respectively. Overall, length of stay was significantly shorter in the rivaroxaban group, compared with the enoxaparin/VKA group across all analyses performed (p < 0.0001). Across regions, the observed admission rates and length of stay duration varied greatly: Asia had the longest overall hospitalization rates, whereas the lowest rates were reported in North America, Australia and New Zealand. Nevertheless, a consistent trend was observed: length of hospital stay in patients with DVT or PE receiving rivaroxaban was shorter than, or at least similar to, patients receiving enoxaparin/VKA.. A single-drug regimen with rivaroxaban may reduce the burden on healthcare systems and patients, and provides effective and well tolerated treatment. The studies shared an open-label design that allowed comparison of initial hospitalization, but limitations include the well monitored clinical trial setting in which decisions on admission and discharge could vary from real-world management.

Topics: Anticoagulants; Enoxaparin; Female; Humans; Length of Stay; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thrombosis; Vitamin K

To evaluate the safety of uninterrupted rivaroxaban, a novel oral anticoagulant that directly inhibits factor Xa, and a vitamin K antagonist (VKA) in eligible adult patients with nonvalvular AF (NVAF) who are scheduled for a catheter ablation.. This is a prospective, randomized, open-label, active-controlled, global multicenter safety study of up to 250 randomized patients. Eligible patients with paroxysmal or persistent NVAF, a left ventricular ejection fraction >40 %, and a creatinine clearance >50 mL/min will be randomized 1:1 to rivaroxaban 20 mg orally once daily or to dose-adjusted oral VKA (recommended international normalized ratio (INR) 2.0-3.0) and stabilized on anticoagulation therapy for 1-7 days (if no intracardiac thrombus on transesophageal echocardiogram (TEE) immediately prerandomization/post-randomization or if 3 weeks of sufficient anticoagulation is documented) or for 4-5 weeks (if no TEE, no documented 3 weeks of sufficient anticoagulation, or by patient choice). During catheter ablation, heparin will be administered (ACT-targeted range = 300-400 s) after catheter ablation, and VKA will be managed per usual care. The next dose of rivaroxaban will be provided at least 6 h after establishment of hemostasis. The primary endpoint will be the incidence of post-procedure major bleeding events observed during the first 30 ± 5 days post-ablation. Secondary endpoints will include post-procedure thromboembolic events, additional bleeding, time-to-event, and medication adherence.. This study is intended to provide information about the safety characteristics of rivaroxaban in patients with NVAF undergoing catheter ablation.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Patient Safety; Postoperative Care; Preoperative Care; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Statistics, Nonparametric; Survival Rate; Thiophenes; Treatment Outcome; Venous Thrombosis; Vitamin K; Warfarin

A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.. In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.. Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups.. A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

Topics: Administration, Oral; Aged; Anticoagulants; Drug Therapy, Combination; Enoxaparin; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Pulmonary Embolism; Recurrence; Rivaroxaban; Thiophenes; Treatment Outcome; Vitamin K

Deep vein thrombosis and its most dangerous outcome, pulmonary embolism, are complications with a high incidence in hospitalized patients. In plastic surgery, abdominoplasty is the aesthetic surgery more frequently associated with deep vein thrombosis condition. This study aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after abdominoplasty in patients considered to be at risk.. In a randomized, double-blind study, 40 patients undergoing abdominoplasty were assigned to receive either oral rivaroxaban (10 mg) or oral placebo once daily for 10 days, beginning 6 to 8 hours after surgery.. The study was interrupted after 27 operations due to systematic complications. The population operated on was composed of women with a mean age of 38 years. Most patients were Caucasian (85 percent) and had a mean body mass index of 28. The average overall rate of complications was 29.6 percent (large hematomas requiring drainage), and all complications were seen in the study group, with none in the control group.. Plastic surgery procedures in which large detachment is planned in patients with a moderate risk of deep venous thrombosis should be evaluated with regard to the risk and benefit of thromboembolism prophylaxis. Other measures must be applied and eventually contraindicate a surgical procedure. Further research is needed to complement the data from this work.

Topics: Abdominoplasty; Administration, Oral; Adult; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Follow-Up Studies; Hematoma; Humans; Middle Aged; Morpholines; Postoperative Care; Postoperative Complications; Postoperative Hemorrhage; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Patients with acute medical illnesses are at increased risk of venous thromboembolism (VTE), a significant cause of morbidity and mortality. Thromboprophylaxis is recommended in these patients but questions remain regarding the optimal duration of therapy. The aim of this study is to determine whether oral rivaroxaban is non-inferior to standard-duration (approximately 10 days) subcutaneous (s.c.) enoxaparin for the prevention of VTE in acutely ill medical patients, and whether extended-duration (approximately 5 weeks) rivaroxaban is superior to standard-duration enoxaparin. Patients aged 40 years or older and hospitalized for various acute medical illnesses with risk factors for VTE randomly receive either s.c. enoxaparin 40 mg once daily (od) for 10 ± 4 days or oral rivaroxaban 10 mg od for 35 ± 4 days. The primary efficacy outcomes are the composite of asymptomatic proximal deep vein thrombosis (DVT), symptomatic DVT, symptomatic non-fatal pulmonary embolism (PE), and VTE-related death up to day 10 + 4 and up to day 35 + 4. The primary safety outcome is the composite of treatment-emergent major bleeding and clinically relevant non-major bleeding. As of July 2010, 8,101 patients from 52 countries have been randomized. These patients have a broad range of medical conditions: approximately one-third were diagnosed with acute heart failure, just under one-third were diagnosed with acute infectious disease, and just under one-quarter were diagnosed with acute respiratory insufficiency. MAGELLAN will determine the efficacy, safety, and pharmacological profile of oral rivaroxaban for the prevention of VTE in a diverse population of medically ill patients and the potential of extended-duration therapy to reduce incidence of VTE.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Female; Heart Failure; Humans; Infections; Male; Middle Aged; Morpholines; Pulmonary Embolism; Respiratory Insufficiency; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.. We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.. The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).. Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).

Topics: Acenocoumarol; Acute Disease; Administration, Oral; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Injections, Subcutaneous; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty.. In this randomized, double-blind study, we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery, plus a placebo tablet or injection. The primary efficacy outcome was the composite of deep-vein thrombosis (either symptomatic or detected by bilateral venography if the patient was asymptomatic), nonfatal pulmonary embolism, or death from any cause at 36 days (range, 30 to 42). The main secondary efficacy outcome was major venous thromboembolism (proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death from venous thromboembolism). The primary safety outcome was major bleeding.. A total of 3153 patients were included in the superiority analysis (after 1388 exclusions), and 4433 were included in the safety analysis (after 108 exclusions). The primary efficacy outcome occurred in 18 of 1595 patients (1.1%) in the rivaroxaban group and in 58 of 1558 patients (3.7%) in the enoxaparin group (absolute risk reduction, 2.6%; 95% confidence interval [CI], 1.5 to 3.7; P<0.001). Major venous thromboembolism occurred in 4 of 1686 patients (0.2%) in the rivaroxaban group and in 33 of 1678 patients (2.0%) in the enoxaparin group (absolute risk reduction, 1.7%; 95% CI, 1.0 to 2.5; P<0.001). Major bleeding occurred in 6 of 2209 patients (0.3%) in the rivaroxaban group and in 2 of 2224 patients (0.1%) in the enoxaparin group (P=0.18).. A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. (ClinicalTrials.gov number, NCT00329628.)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

We investigated the efficacy of rivaroxaban, an orally active direct factor Xa inhibitor, in preventing venous thrombosis after total knee arthroplasty.. In this randomized, double-blind trial, 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban, 10 mg once daily, beginning 6 to 8 hours after surgery, or subcutaneous enoxaparin, 40 mg once daily, beginning 12 hours before surgery. The primary efficacy outcome was the composite of any deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause within 13 to 17 days after surgery. Secondary efficacy outcomes included major venous thromboembolism (i.e., proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death related to venous thromboembolism) and symptomatic venous thromboembolism. The primary safety outcome was major bleeding.. The primary efficacy outcome occurred in 79 of 824 patients (9.6%) who received rivaroxaban and in 166 of 878 (18.9%) who received enoxaparin (absolute risk reduction, 9.2%; 95% confidence interval [CI], 5.9 to 12.4; P<0.001). Major venous thromboembolism occurred in 9 of 908 patients (1.0%) given rivaroxaban and 24 of 925 (2.6%) given enoxaparin (absolute risk reduction, 1.6%; 95% CI, 0.4 to 2.8; P=0.01). Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin (P=0.005). Major bleeding occurred in 0.6% of patients in the rivaroxaban group and 0.5% of patients in the enoxaparin group. The incidence of drug-related adverse events, mainly gastrointestinal, was 12.0% in the rivaroxaban group and 13.0% in the enoxaparin group.. Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar rates of bleeding. (ClinicalTrials.gov number, NCT00361894.)

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

An effective and safe oral anticoagulant that needs no monitoring for dose adjustment is urgently needed for the treatment of diseases that require long-term anticoagulation. Rivaroxaban (BAY 59-7939) is an oral direct factor Xa inhibitor currently under clinical development.. This randomized, parallel-group phase II trial in patients with proximal deep-vein thrombosis explored the efficacy and safety of rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily compared with enoxaparin 1 mg/kg BID followed by vitamin K antagonist. Each treatment was administered for 12 weeks. The primary efficacy end point was an improvement in thrombotic burden at day 21 (assessed by quantitative compression ultrasonography; > or = 4-point improvement in thrombus score) without recurrent symptomatic venous thromboembolism or venous thromboembolism-related death. The primary safety end point was major bleeding during 12 weeks of treatment. Outcomes were adjudicated centrally without knowledge of treatment allocation. The primary efficacy end point was achieved in 53 (53.0%) of 100, 58 (59.2%) of 98, 62 (56.9%) of 109, and 49 (43.8%) of 112 patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively, compared with 50 (45.9%) of 109 patients treated with enoxaparin/vitamin K antagonist. There was no significant trend in the dose-response relationship between rivaroxaban BID and the primary efficacy end point (P=0.67). Major bleeding was observed in 1.7%, 1.7%, 3.3%, and 1.7% of patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively. There were no major bleeding events with enoxaparin/vitamin K antagonist.. Results of this proof-of-concept and dose-finding study support phase III evaluation of the orally active direct factor Xa inhibitor rivaroxaban, because efficacy and safety were apparent in the treatment of proximal deep-vein thrombosis across a 3-fold range of fixed daily dosing.

Topics: Administration, Oral; Adult; Anticoagulants; Factor Xa Inhibitors; Heparin; Humans; Morpholines; Patient Selection; Pulmonary Embolism; Rivaroxaban; Safety; Thiophenes; Thrombosis

Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants.. To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor--BAY 59-7939--relative to enoxaparin in patients undergoing elective total hip replacement.. In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5-9 days after surgery.. Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose-response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin.. When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5-10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Dose-Response Relationship, Drug; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes; Thromboembolism; Venous Thrombosis

We assessed the effectiveness and safety of rivaroxaban in patients with isolated distal deep vein thrombosis (IDDVT).. Symptomatic venous thromboembolism (VTE) and major bleeding were assessed.. Short-term, low-dose rivaroxaban seems safe and effective for IDDVT treatment.

Topics: Acute Disease; Anticoagulants; Hemorrhage; Humans; Japan; Prospective Studies; Pulmonary Embolism; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Dyspnea; Female; Humans; Leukocyte Count; Middle Aged; Pulmonary Embolism; Rivaroxaban

Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance.. A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3).. In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.

Topics: Anticoagulants; COVID-19; Decision Making; Fibrinolytic Agents; Hemorrhage; Humans; Iran; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism; Venous Thrombosis; Warfarin

Ageno W, Bertu L, Bucherini E, et al; RIDTS study group.

Topics: Anticoagulants; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

The aim: To assess the effectiveness of thrombolytic therapy in treatment pulmonary embolism.. Materials and methods: The work analyzed the results of the survey and conservative treatment of 284 patients with pulmonary embolism treated in cardiological department in «Uzhgorod Central City Clinical Hospital» during 2019-2022. Patients were divided into two groups: group I - 250 (88%) patients received anticoagulant therapy; group II - 34 (12%) patients received thrombolytic therapy that was then switched to new oral anticoagulants.. Results: In I group, the first three days were carried out continuously intravenous infusion of heparin in a dose of 25-30 thousand units per day, on the fourth day switched to subcutaneous injection for 10-14 days with subsequent switching to rivaroxaban. 34 (12.0%) patients of the II group, was started with thrombolytic therapy. 32 (94.1%) patients were prescribed alteplase 100 mg/day, and 2 (5.9%) patients - streptokinase 1.5 million units/day. After thrombolysis, patients were prescribed rivaroxaban for prolonged period. Thrombolytic therapy made it possible to prevent fatal cases, and in monotherapy with anticoagulants - mortality was 4.8%. Minor hemorrhagic complications like hematuria, local hematomas at the injection site, bleeding gums were observed in 7.6% of patients during thrombolytic therapy. No cases of large hemorrhages were observed. Manifestations of chronic postembolic pulmonary hypertension in the distant period were found in 97.1% and 6.9% of patients of the I and II groups, respectively. Lethality in the remote period was 5.3% - all in the 1st group of patients due to PE recurrence and acute myocardial infarction.. Conclusions: Implementation of thrombolytic therapy in patients with thromboembolism of the pulmonary artery allows effectively prevent recurrence with a fatal outcome, restore the lumen of the pulmonary arteries and prevent the development of chronic postembolic pulmonary hypertension in the immediate and remote period of observation compared to isolated anticoagulant therapy.

Topics: Anticoagulants; Hemorrhage; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Rivaroxaban; Thrombolytic Therapy; Treatment Outcome

We present a female patient with a history of systolic heart failure with an ejection fraction of 25-30%, and unprovoked pulmonary embolism on extended anticoagulation therapy with rivaroxaban who underwent a pericardial window for cardiac tamponade due to hemopericardium in the setting of direct oral anticoagulant (DOAC). The rivaroxaban was held following the pericardial window, and she experienced another episode of pulmonary embolism before the rivaroxaban could be restarted. Currently, there are no guidelines on when to restart anticoagulation postpericardial window for DOAC-associated hemopericardium. Studies are needed to help solve this dilemma.. We present a female patient with a history of systolic heart failure which means their left ventricle was unable to pump blood efficiently. They also have a history of an unprovoked disruption in the flow of blood in the pulmonary arteries or its branches, known as a pulmonary embolism. The patient was on direct oral anticoagulation medication to thin their blood, promoting efficient blood flow and minimizing the risk of clots and blockages. While on this medication, the patient developed a significant collection of blood around the heart, so the medication was withheld and the blood collection was drained. She developed another episode of pulmonary embolism before the medication could be restarted. Healthcare providers need guidance on when to restart anticoagulation medications in these types of patients.

Topics: Anticoagulants; Female; Humans; Pericardial Effusion; Pulmonary Embolism; Rivaroxaban; Thromboembolism; Venous Thromboembolism

The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period.. XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.

Topics: Aged; Anticoagulants; Hemorrhage; Humans; Japan; Product Surveillance, Postmarketing; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

The aim of this study was to analyze the clinical characteristics and treatment of children with Mycoplasma pneumoniae pneumonia (MPP) who also present with pulmonary embolism (PE).. This retrospective analysis examined the demographic data, clinical manifestations, laboratory tests, imaging characteristics, therapy, and prognosis of nine cases of children with Mycoplasma pneumoniae pneumonia (MPP) complicated by pulmonary embolism (PE). The study focused on patients admitted to the respiratory department of Tianjin Children's Hospital between January 2018 and December 2021.. The age range of the patients was 3 to 8 years old, with a median age of 7.5 years. The median number of days from pulmonary infection to the diagnosis of embolism was 14 days. All patients had refractory Mycoplasma pneumoniae pneumonia (RMPP). Among them, three patients reported chest pain, one of whom had hemoptysis, while five patients had dyspnea, and six patients experienced radiating pain at unusual sites. Five out of the nine children tested positive for lupus anticoagulant (LA), five for anticardiolipin antibody (ACA), three for anti-2-glycoprotein antibody IgM, four for reduced protein S or protein C activity, and three for elevated coagulation factor VIII. Moreover, six out of the nine children tested positive for antinuclear antibodies. All the children underwent CT pulmonary angiograms, which revealed filling defects. After sequential low-molecular heparin anticoagulation with rivaroxaban, nine children in this study showed a good prognosis, with two of them receiving thrombolytic therapy for combined cardiac embolism. Follow-up at 0.5-9 months showed the gradual resolution of the emboli in all 9 children, with no thrombotic recurrences and normalized autoantibodies and thrombophilia markers.. The majority of cases involving Mycoplasma pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) were diagnosed with refractory MPP (RMPP). However, PE did not always occur in the advanced stages of the disease. Most patients presented with transient autoantibody positivity, abnormal coagulation, and fibrinolytic balance. With timely treatment, the prognosis of MPP combined with PE is generally good. Additionally, rivaroxaban treatment has been shown to be safe and effective.

Topics: Child; Child, Preschool; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Pulmonary Embolism; Retrospective Studies; Rivaroxaban

This study aimed to assess the appropriateness of direct oral anticoagulants (DOACs) utilization in a Saudi tertiary hospital.. Adult inpatients and outpatients diagnosed with atrial fibrillation, deep vein thrombosis, or pulmonary embolism were included in a retrospective cohort study. Patients received at least one month of apixaban, rivaroxaban, or dabigatran. The duration of the study at the Armed Forces Hospital Southern Region in Khamis Mushait, Saudi Arabia, was from January 1, 2019, to December 31, 2021. The study assessed the appropriateness of DOACs dosing, initial and follow-up monitoring, the presence of clinically significant interactions, and treatment duration adherence.. 778 patients were included in the analysis (mean age 71.34 ± 15.98 years, equal male and female representation). Rivaroxaban was administered to 40.8% of the patients, while apixaban and dabigatran were administered to 31.02% and 28.18% of the patients, respectively. The most prevalent indication for DOACs was atrial fibrillation (72.84%), followed by deep vein thrombosis and pulmonary embolism (27.16%). The most prevalent category of medication errors was inappropriate maintenance dose (41.7%), followed by inappropriate initial dose (37.97%) and lack of laboratory parameter monitoring (36.42%). 31.5 percent of the study sample lacked baseline renal functions, while 24.5% of patients lacked baseline liver functions. 115 patients (14.8%) had potential clinically significant interactions. Regarding treatment duration, 232 patients (29.8%) were improperly prescribed DOACs based on their indications.. In a significant proportion of DOAC patients, the prescribed rational DOAC utilization parameters were not implemented. The results of the study provide specific improvement areas and objectives for Anticoagulation stewardship programs.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Saudi Arabia; Stroke; Tertiary Care Centers; Venous Thrombosis

Thrombotic complications are common in patients with severe COVID-19 pneumonia with important consequences on the diagnostic and therapeutic management. We report a consecutive series of five patients on long-term oral anticoagulation therapy who presented to our hospital for severe COVID-19 pneumonia associated with segmental acute pulmonary embolism despite adherence to therapy and with an adequate anticoagulant range at the time of the event. Four patients were receiving a direct oral anticoagulant (two with edoxaban, one with rivaroxaban and one with apixaban) and one patient a vitamin K antagonist. No significant thrombotic risk factors, active cancer, or detectable venous thromboembolism were present. In all cases, elevated d-dimer and fibrinogen levels with a parallel rise in markers of inflammation were documented. The combination of these findings seems to support the hypothesis that considers the local vascular damage determined by severe viral infection as the main trigger of thrombi detected in the lungs, rather than emboli from peripheral veins.

Topics: Anticoagulants; COVID-19; COVID-19 Drug Treatment; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

 Data from clinical trials indicate that direct oral anticoagulants (DOACs) are noninferior and safer than conventional therapy (low-molecular-weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting..  This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013 to 2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional hazards regression was used to estimate adjusted hazard ratios of the endpoints..  A total of 58,137 patients were included (10,775 VKAs, 10,440 apixaban, 36,922 rivaroxaban). Propensity score-matched cohort sizes were 7,503 for apixaban and 9,179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32-0.59]), all-cause death (0.61 [0.51-0.74]), and first recurrent VTE (0.67 [0.52-0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53-0.74]) but not for bleeding requiring hospitalization (0.86 [0.69-1.07]) or first recurrent VTE (0.91 [0.74-1.13])..  Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.

Topics: Administration, Oral; Adult; Anticoagulants; Cohort Studies; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

The role of the right to left ventricular (RV/LV) diameter ratio in predicating long-term outcomes in patients with pulmonary thromboembolisms (PTEs) treated with direct oral anticoagulants is unclear.We investigated the association between the RV/LV diameter ratio and clinical outcomes in PTE patients under rivaroxaban from the data of a multicenter, prospective, observational study (J'xactly Study) in Japanese patients with acute venous thromboembolisms (VTEs) including deep vein thromboses, PTEs, or both. Of a total of 1,039 patients with an acute VTE (from December 2016 to April 2018), 429 were diagnosed with PTEs, however, the population in this study consists of 216 patients in whom the RV/LV diameter ratio measured on the axial CT or transthoracic echocardiogram was available.The RV/LV diameter ratio increased significantly with the severity of the PTE classification (nonmassive 0.79 [0.67-0.93], submassive 1.10 [0.83-1.31], massive 1.13 [0.94-1.19], arrest or collapse 1.38 [0.66-2.38], P < 0.001). During a median follow-up of 624 (550-690) days, a sum of the composite adverse events including recurrent VTEs, acute coronary syndrome, ischemic strokes, death from any cause, or major bleeding events occurred in 26 patients (12.0%, 7.58 events per 100 patient-years). Multivariate analysis revealed that an RV/LV diameter ratio ≥ 1.0 had no association with the incidence of composite adverse events (HR 1.34, 95% confidence interval 0.59-2.91, P = 0.48).In summary, in Japanese PTE patients under rivaroxaban, the RV/LV diameter ratio measured on the CT or transthoracic echocardiogram was associated with the PTE severity, but not with the clinical outcomes.

Topics: Acute Disease; Heart Ventricles; Humans; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Several cases of venous thromboembolism in patients treated with direct oral anticoagulants (DOACs) have been reported in the literature, but a quantative analysis of postmarketing reports is lacking. The objective of this study was to determine the post-marketing odds ratio (OR) and reporting odds ratio (ROR) of venous thromboembolism in patients receiving DOACs compared among each other and to vitamin K antagonists (VKAs).. The OR and ROR were used to determine the ratio of reports for deep vein thrombosis and pulmonary embolism between 1 January, 2012 and 15 November, 2020 using the World Health Organization VigiLyze database. This was performed using all venous thromboembolism events in which a DOAC or a VKA was the suspected medication. The OR and ROR including 95% confidence intervals were calculated for each DOAC drug in comparison to all VKAs as a group.. The OR of deep vein thrombosis was highest for rivaroxaban compared with dabigatran and apixaban [2.63 (2.41-2.89); 1.84 (1.72-1.97)]. The OR of deep vein thrombosis was lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.44 (0.32-0.61); 0.31 (0.22-0.42); 0.17 (0.12-0.23)]. The OR of pulmonary embolism was also highest for rivaroxaban compared with dabigatran and apixaban [2.59 (2.37-2.83); 1.79 (1.68-1.92)]. The OR of pulmonary embolism was also lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.77 (0.60-0.97); 0.59 (0.41-0.67); 0.30 (0.23-0.37)]. Comparing RORs of various DOACs with VKAs, rivaroxaban had the highest RORs for deep vein thrombosis/pulmonary embolism, in comparison to apixaban, dabigatran and edoxaban.. Our findings may indicate a higher association between rivaroxaban therapy and venous thromboembolism as compared with apixaban, dabigatran and edoxaban. These findings are uncertain owing to the reliability of a post-marketing registration system that is negatively influenced by a high level of under-reporting. However, based on pharmacodynamics, we cannot exclude the possibility that there is a real effect that may be driven by non-adherence.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pulmonary Embolism; Pyridones; Reproducibility of Results; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; World Health Organization

Topics: Anticoagulants; Arm; Dyspnea; Edema; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Rivaroxaban; Treatment Outcome

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Infant; Insurance Claim Review; Pulmonary Embolism; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism; Warfarin

BACKGROUND We present the report of the first case, to the best of our knowledge, of central retinal vein occlusion (CRVO) that occurred 3 days after anticoagulation discontinuation in a patient with a history of pulmonary embolism in the course of COVID-19. CASE REPORT A previously healthy 38-year-old man was hospitalized in April 2021 with severe COVID-19 pneumonia, complicated by segmental and subsegmental pulmonary embolism. The patient was treated with a concurrent combination of remdesivir, dexamethasone, therapeutic enoxaparin, ceftriaxone, passive oxygen therapy, and convalescent plasma therapy, which led to pulmonary improvement. The treatment with therapeutic enoxaparin (80 mg/0.8 mL twice a day) was continued for 1 month after discharge, followed by 15 mg of rivaroxaban twice a day for 3 weeks and 20 mg of rivaroxaban once a day for 11 weeks. Within 3 days after rivaroxaban discontinuation, the patient experienced a decrease in visual acuity in his right eye, to the level of 5/25. Nonischemic CRVO with cystoid macular edema was diagnosed and an intravitreal injection of ranibizumab was performed. Common identifiable factors contributing to CRVO were excluded, and the treatment with prophylactic enoxaparin was initiated. Two weeks later, macular edema decreased significantly and visual acuity improved to 20/20. The treatment with enoxaparin was discontinued. CONCLUSIONS Rebound hypercoagulability after discontinuation of rivaroxaban therapy can manifest as CRVO in a young patient with a history of COVID-19 pulmonary embolism. It was successfully treated with an intravitreal injection of ranibizumab.

Topics: Adult; Angiogenesis Inhibitors; COVID-19; COVID-19 Serotherapy; Enoxaparin; Glucocorticoids; Humans; Intravitreal Injections; Macular Edema; Male; Pulmonary Embolism; Ranibizumab; Retinal Vein Occlusion; Rivaroxaban; Tomography, Optical Coherence; Treatment Outcome

In the last decade, direct oral anticoagulants (DOACs) have been incorporated as an anticoagulation tool in patients with acute pulmonary thromboembolism (PTE). Although they have a better pharmacological profile than vitamin K antagonists (VKA), the use of these drugs is not massive. The objective of this study was to evaluate the use of DOACs in patients with acute PE and to detect determinants of its use.. Prespecified analysis of the CONAREC XX registry that included patients with acute PE in 64 centers in Argentina. An analysis was performed to detect predictors of DOAC prescription at discharge.. 579 patients who received anticoagulation at hospital discharge were analyzed: 60% received VKA, 21% heparin and 19% DOAC (of them, 49% Rivaroxaban, 34% Apixaban, and 17% Dabigatran). Patients receiving DOACs had less severe PE, lower risk of bleeding, and fewer in-hospital complications. At 30-day follow-up, there were no differences in all-cause mortality or bleeding. Health coverage by social insurance (OR 7.45, CI 95% 1.74-31.9, p < 0.01) or by private coverage (OR 10.5, CI 95% 2.4-45.9, p < 0.01) were independent predictors of DOAC prescription at discharge, and history of heart failure (OR 0.19, 95% CI 0.04-0.84, p = 0.028) and oncological disease (OR 0.49, 95% CI 0.27-0.89; p = 0.02) were predictors not prescribe them.. One in five survivors of acute PE received DOACs at hospital discharge in Argentina, and this was determined by clinical and economic variables.. En la última década los anticoagulantes orales directos (ACOD) se incorporaron como herramienta para la anticoagulación en pacientes con tromboembolia pulmonar (TEP) aguda. Aunque tienen un mejor perfil farmacológico que los antagonistas de la vitamina K (AVK), el uso de estos fármacos no es masivo. El objetivo del presente trabajo fue evaluar el uso de ACOD en pacientes con TEP aguda y detectar determinantes de su indicación.. Análisis preespecificado del registro CONAREC XX que incorporó pacientes con TEP aguda en 64 centros de Argentina. Se realizó un análisis para detectar predictores de prescripción de ACOD al alta.. Se analizaron 579 pacientes que recibieron anticoagulación al alta hospitalaria: el 60% recibió AVK, el 21% heparinas y el 19% ACOD (de ellos, un 49% rivaroxabán, un 34% apixabán y un 17% dabigatrán). Los pacientes que recibieron ACOD tenían TEP de menor gravedad, menor riesgo de hemorragia y menos complicaciones intrahospitalarias. En el seguimiento a 30 días no hubo diferencias en mortalidad por todas las causas o sangrados. La cobertura de salud por un seguro social (odds ratio [OR] 7.45; intervalo de confianza del 95% [IC 95%]: 1.74-31.9; p < 0.01) o por cobertura privada (OR 10.5; IC 95%: 2.4-45.9; p < 0.01) fueron predictores independientes de la prescripción de ACOD al alta, y el antecedente de insuficiencia cardiaca (OR 0.19; IC 95%: 0.04-0.84; p = 0.028) y de enfermedad oncológica (OR 0.49; IC 95%: 0.27-0.89; p = 0.02) fueron predictores de no prescribirlos.. Uno de cada cinco supervivientes de TEP aguda recibió ACOD al egreso hospitalario en Argentina, y esto fue determinado por variables clínicas y económicas.

Topics: Acute Disease; Anticoagulants; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban

Kinase inhibitors (KI) and antibodies targeting the VEGF pathway are approved in a broad spectrum of cancers and associated with an increased risk of bleeding and thromboembolic events (TE). The use of direct oral anticoagulants (DOACs) apixaban and rivaroxaban is increasing in cancer patients, but limited data are available for patients receiving anti-VEGF agents.. To assess safety of DOAC with concomitant anti-VEGF agents, a retrospective chart review of all patients receiving concomitantly DOAC and anti-VEGF agents was performed from 2013 to 2020 in our center. Data on demographics, safety, and time on treatment were collected. Main outcome was safety (bleeding and thromboembolic events).. Of 92 patients (median age 66 years (IQR: 59-72)), 40 were treated with KI and 52 with bevacizumab. The most frequent primary tumor sites were colon/rectum (24%), kidney (21%), ovary (13%), lung (11%), soft tissue sarcoma (10%), and thyroid (9%); 2% had brain metastases. Apixaban 5 mg bid (n = 41) or rivaroxaban 20 mg daily (n = 51) were given for TE (65%), atrial fibrillation (32%), or other indications (3%). The median duration of concomitant treatment was 4.8 months (95%CI: 0.7-50.0) with bevacizumab and 11.7 months (95%CI: 0.1-53.8) with KI. Grade ≥ 3 bleeding events occurred in 5 patients (5%): 4 patients receiving bevacizumab (one grade 5 upper digestive tract bleeding and three grade 3 rectal or vaginal hemorrhages) and 1 patient under cabozantinib for kidney cancer with endobronchial metastasis (grade 3 hemoptysis). Grade ≥ 3 TE occurred in 8 patients (9%): 7 patients receiving bevacizumab (including one grade 5 pulmonary embolism), and one patient receiving sunitinib (grade 3 pulmonary embolism). Median time-to-event (bleeding or thrombotic event) was not reached (NR) (95%CI: 76.9-NR) for KI and 86.9 months (95%CI: 42.9-148.0) for bevacizumab. CONCLUSIONS AND RELEVANCE: In our experience, the use of DOAC was safe in selected patients treated with KI, but unclear with bevacizumab. More data are needed to endorse guidelines in this specific group of patients.

Topics: Administration, Oral; Aged; Anticoagulants; Bevacizumab; Dabigatran; Female; Hemorrhage; Humans; Neoplasms; Pulmonary Embolism; Retrospective Studies; Rivaroxaban

Sickle cell disease (SCD) is a hematological disorder characterized by sickling of red blood cells. Patients are at increased risk of venous thromboembolism. There are no guidelines for the management of venous thromboembolism in sickle cell disease specifically in terms of the anticoagulant of choice.. Here, we report a case of a 30-year-old lady with past medical history of sickle cell disease who came with chest pain and shortness of breath.. We found that she has bilateral pulmonary embolism (PE).. She was started on rivaroxaban.. The patient was followed for 18 months, she did not suffer from recurrence of PE, and she did not develop any complications related to rivaroxaban.. We concluded that rivaroxaban is effective in treating PE in sicklers and also it is safe.

Topics: Adult; Anemia, Sickle Cell; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

A 73-year-old woman took a chest radiography for medical check-up, and pulmonary cement embolism was diagnosed. She had undergone percutaneous vertebroplasty. Ventilation-perfusion imaging revealed V/Q mismatched perfusion defect on the lung. Then, she has taken rivaroxaban (orally active direct factor Xa inhibitor) for 6 months and took follow-up V/Q scan. It revealed the disappearance of previous 2 of 3 moderate V/Q mismatches. There are controversies in the role of anticoagulation in treatment of pulmonary cement embolism, and this case shows functional recovery through the perfusion scan after anticoagulation treatment.

Topics: Aged; Humans; Male; Pulmonary Embolism; Rivaroxaban; Tomography, Emission-Computed, Single-Photon; Ventilation-Perfusion Ratio

Topics: Chemical and Drug Induced Liver Injury; Factor Xa Inhibitors; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban

Topics: Anticoagulants; Developing Countries; Factor Xa Inhibitors; Humans; Length of Stay; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Pulmonary embolism (PE) is a life-threatening disease, which accounts for the major type of venous thromboembolism. Currently, there is limited understanding and management for PE. Rivaroxaban is reported to treat patients with PE. However, there is still insufficient evidence on rivaroxaban for the treatment of Chinese patients with acute PE. Thus, this retrospective study investigated the benefits and safety of rivaroxaban for Chinese patients with acute PE.A total of 72 Chinese patient cases with acute PE were analyzed in this study. Of these, 36 cases who received rivaroxaban mono-therapy were assigned to the treatment group, while the remaining 36 cases who received standard therapy were assigned to the control group. The benefits were assessed by the duration of hospital stay, treatment satisfaction, and safety.After treatment, rivaroxaban mono-therapy showed better benefits in decreasing the duration of hospital stay (P < .01), increasing treatment satisfaction (P < .01), and reducing mild bleeding (P = .02) in Chinese patients with acute PE, than standard therapy.The results of this study indicated that rivaroxaban may provide more benefits than the standard therapy for Chinese patients with acute PE. Future studies are still needed to warrant the current results.

Topics: Acute Disease; China; Factor Xa Inhibitors; Female; Humans; Length of Stay; Male; Middle Aged; Patient Satisfaction; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Treatment Outcome

To compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE).. Consecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB).. In the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37).. Apixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer.. ClinicalTrials.gov identifier: NCT03504007.

Topics: Enoxaparin; Factor Xa Inhibitors; Female; Gastrointestinal Neoplasms; Hemorrhage; Humans; Liver Neoplasms; Male; Middle Aged; Outcome and Process Assessment, Health Care; Pancreatic Neoplasms; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Severity of Illness Index; United States; Venous Thrombosis

Residual perfusion defects (RPD) as detected by lung scintigraphy occur in over 50% of patients with acute pulmonary embolism (PE) treated with vitamin K antagonists but there is lack of data in patients treated with direct oral anticoagulants. The aim of this retrospective study was to estimate the incidence of RPD detected by ventilation perfusion (VQ) scan at 3-6 months in patients with first acute symptomatic PE treated with rivaroxaban compared to warfarin. Consecutive eligible patients treated with rivaroxaban as part of a previous study were identified. The Monash Health Radiology database was used to identify a historical cohort of age matched (± 5 years) patients treated with warfarin. Follow-up VQ scans were classified as normal (no perfusion defect) or abnormal (matched or unmatched perfusion defects) by two independent nuclear medicine physicians blinded to treatment. Any disagreement was resolved by consensus. One hundred and ninety patients with PE (95 in each cohort) were included (mean age 56.8 years; 41.1% males; 54.2% unprovoked). In the overall cohort, 31.1% had RPD with a significantly lower incidence of RPD in rivaroxaban treated patients 23.2% (95% CI 15.8-32.6), compared to warfarin 38.9% (95% CI 29.8-49.0). Treatment with rivaroxaban was associated with a significantly lower incidence of RPD detected by VQ scan at 3-6 months compared to warfarin. This supports recent in-vitro data suggesting an indirect enhancement of fibrinolysis by direct oral Xa inhibitors but requires confirmation in larger studies.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Cohort Studies; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Lung; Male; Middle Aged; Perfusion Imaging; Pulmonary Embolism; Radionuclide Imaging; Retrospective Studies; Rivaroxaban; Treatment Outcome; Warfarin

Studies on the use of direct oral anticoagulants (DOACs) in obese patients are limited. Current guidelines advise against DOAC use in patients with a body weight more than 120 kg or body mass index higher than 40 kg/m. Retrospective matched cohort study.. Integrated delivery system of 40 academic, community, and specialty hospitals.. A total of 1840 adults with a primary admission diagnosis of acute VTE who received a DOAC (apixaban, dabigatran, or rivaroxaban [632 patients] or warfarin [1208 patients]) while hospitalized between January 1, 2011, and October 1, 2015, and who had a body weight more than 100 kg and less than 300 kg, were included. Patients in the warfarin group were matched in a 2:1 ratio to patients who received a DOAC based on history of VTE, chronic kidney disease, race, and age.. The primary outcome was recurrence of VTE within 12 months of the index admission date. Secondary outcomes included occurrence of pulmonary embolism (PE) and deep vein thrombosis (DVT) events separately within the study time frame, as well as bleeding within 12 months of the index admission date. No significant difference in the recurrence of VTE was observed between patients who received a DOAC compared with those who received warfarin (6.5% vs 6.4%, p=0.93). Likewise, no significant differences in the occurrence of PE and DVT were seen between the DOAC- and warfarin-treated patients (3.7% vs 3.8%, p=0.94, and 3% vs 3.5%, p=0.56, respectively). Bleeding occurred in 1.7% and 1.2% of patients in the DOAC and warfarin groups, respectively (p=0.31).. To our knowledge, this is the largest clinical study to date showing that patients with obesity can be treated effectively and safely with a DOAC compared with warfarin for acute VTE. Thus DOACs should be considered a reasonable alternative to warfarin for treatment of acute VTE in obese patients.

Topics: Administration, Oral; Aged; Anticoagulants; Cohort Studies; Dabigatran; Female; Humans; Male; Middle Aged; Obesity, Morbid; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

To conduct a survey of diagnostic facility and therapeutic capability of Pulmonary thromboembolism (PE) in 90 hospitals throughout China.. It was a cross-sectional study among the participating hospitals of the National Key Research & Development Program of China-the Precision Research of Standardized Management and Application of Pulmonary Thromboembolism to obtain the equipment and application of radiological facility to diagnose PE, laboratory tests for thrombophilia, coagulation function and the availability of anticoagulants and thrombolysis agents.. CT pulmonary arteriography is capable in all 90 hospitals, 71.11% of the hospitals could perform ventilation/perfusion scintigraphy, 24.44% of the hospitals do not routinely perform right heart evaluation by echocardiography. Protein C and protein S activity can be detected in half of the hospitals and warfarin pharmacogenomics tests can be conducted in 40 hospitals. Immune turbidimetry was used as the detection method of D-dimer in 72.37% hospitals. About 81.11% of participating hospitals were equipped with new novel oral anticoagulants, all of which were equipped with Rivaroxaban.. The hospitals are capable for standardized diagnosis and management PE, while the capability of precise stratification, coagulation function tests, thrombophilia screening and pharmacogenomics requires further improvement.

Topics: Angiography; Anticoagulants; Blood Coagulation Tests; China; Cross-Sectional Studies; Echocardiography; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Hospital Bed Capacity; Hospitals; Humans; Nephelometry and Turbidimetry; Patient Care Management; Pharmacogenetics; Pulmonary Embolism; Rivaroxaban; Surveys and Questionnaires; Thrombophilia; Ventilation-Perfusion Scan; Warfarin

As a single agent, fluorouracil has been documented to have a small but present chance of causing extravasation of the port when not properly administered. It has also been shown that cancer patients receiving chemotherapy are at increased risk of deep vein thrombosis, symptomatic or silent.. A 43-year-old male patient with stage III colon cancer receiving FOLFOX developed a saddle pulmonary embolism involving possible extravasation that was discovered following cycle 3 of chemotherapy. CT scan and lower extremity Doppler confirmed non-occlusive deep vein thrombosis along with saddle pulmonary embolism.. Fluorouracil, an inflammitant, has been shown to have damaging potential, especially in terms of the integrity of the endothelium. Over time, this can lead to serious complications such as cardiotoxicity, including deep vein thrombosis formation. Based on how and when the thrombi were discovered, it is not possible to deduce whether the port, the 5-FU, extravasation or other factors were the precipitators of the formation of the thrombi. The combination of chemotherapy treatment along with CVC placement appears to have an additive risk to the formation of a thrombus. Practitioners should take caution when evaluating for extravasation and CVC integrity and note other potential differentials for causes, including deep vein thrombosis/saddle pulmonary embolism formation.

Topics: Adult; Fluorouracil; Humans; Lower Extremity; Male; Pulmonary Embolism; Rivaroxaban; Thrombosis; Tomography, X-Ray Computed

An 81-year-old man presented with shortness of breath and was referred to our hospital with suspected acute pulmonary embolism. Enhanced computed tomography revealed a right aberrant subclavian artery with a thrombosed Kommerell diverticulum (KD), as well as deep vein thrombosis in the left leg and bilateral pulmonary artery thrombosis. Thrombosis in the KD disappeared after one month of anticoagulation treatment with rivaroxaban. Thrombosis of a KD is a rare condition that may cause distal emboli and subclavian steal syndrome, although this syndrome was not present in this case. Rivaroxaban is an effective anticoagulant for treating thrombosis of a KD.

Topics: Aged, 80 and over; Anticoagulants; Cardiovascular Abnormalities; Diverticulum; Humans; Male; Pulmonary Embolism; Rivaroxaban; Subclavian Artery; Thrombosis; Tomography, X-Ray Computed

The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.. In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.. A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.. These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Topics: Administration, Oral; Adult; Age Distribution; Aged; Anticoagulants; Asia; Comorbidity; Cross-Sectional Studies; Dabigatran; Diabetes Mellitus; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension; Latin America; Male; Middle Aged; Middle East; Neoplasms; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries

We report 3 patients with coronavirus disease who had a decline in respiratory status during their hospital course that responded well to intravenous steroids and interleukin-6 receptor antagonist therapy. These patients later showed development of persistent hypoxia with increased levels of d-dimer levels and were given a diagnosis of pulmonary embolisms.

Topics: Acute Disease; Aged; Antibodies, Monoclonal, Humanized; Anticoagulants; Betacoronavirus; Biomarkers; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Cytokine Release Syndrome; Enoxaparin; Female; Fibrin Fibrinogen Degradation Products; Humans; Hypoxia; Male; Methylprednisolone Hemisuccinate; Middle Aged; Pandemics; Pneumonia, Viral; Pulmonary Embolism; Rivaroxaban; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

The full spectrum of COVID-19 is still emerging, although several studies have highlighted that patients infected with the novel coronavirus can potentially develop a hypercoagulable state. However, several aspects related to the incidence and pathophysiology of the association between COVID-19 and pulmonary embolism are not well established. Here, we present a case of a patient with COVID-19 who developed acute pulmonary embolism. Clinical and laboratory data and findings of non-enhanced CT indicate possibility of acute pulmonary embolism, and support the decision to proceed with computed tomography pulmonary angiography that can objectively identify filling defects in pulmonary arterial branches.

Topics: Acute Disease; Betacoronavirus; Computed Tomography Angiography; Humans; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; SARS-CoV-2

The Coronavirus Disease 2019 (COVID 19) has been reported in almost every country in the world. Although a large proportion of infected individuals develop only mild symptoms or are asymptomatic, the spectrum of the disease among others has been widely variable in severity. Additionally, many infected individuals were found to have coagulation markers abnormalities. This is especially true among those progressing to severe pneumonia and multi-organ failure. While the incidence of venous thromboembolic (VTE) disease has been recently noted to be elevated among critically ill patients, the incidence among ambulatory and non-critically ill patients is not yet clearly defined. Herein, we present six patients who didn't have any hypercoagulable risk factors yet presented with pulmonary embolism in association with COVID 19 infection. Furthermore, we discuss the possible underlying mechanisms of hypercoagulability and highlight the possibility of underdiagnosing pulmonary embolism in the setting of overlapping symptoms, decreased utilization of imaging secondary to associated risks, and increased turnover times. In addition, we emphasize the role of extended thromboprophylaxis in discharged patients.

Topics: Adult; Aged; Anticoagulants; Betacoronavirus; Coronavirus Infections; COVID-19; Enoxaparin; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; SARS-CoV-2; Tissue Plasminogen Activator

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by the triad of nose bleeding, telangiectasia and familial heredity.. We report the case of a patient who had idiopathic venous cerebral thrombosis complicated by a cerebral infarction treated with warfarin. In the context of a psoas hematoma by warfarine overdose and immobilization, the patient had deep vein thrombosis of the left lower limb with pulmonary embolism revealing a pulmonary arteriovenous malformation. After a reexamination, the patient clinical phenotype of HHT was confirmed genetically. The patient was treated with rivaroxaban allowing clinical improvement and partial recanalization of all thrombosis after six months. Thrombotic overisk has already been studied in HHT patients but the use of anticoagulants is at higher risk in these patients. However this patient experienced no adverse event with rivaroxaban.. This is the first case described of cerebral venous thrombosis treated with rivaroxaban revealing an HHT.

Topics: Anticoagulants; Arteriovenous Fistula; Delayed Diagnosis; Diagnosis, Differential; Humans; Intracranial Thrombosis; Late Onset Disorders; Magnetic Resonance Imaging; Male; Middle Aged; Pulmonary Artery; Pulmonary Embolism; Pulmonary Veins; Rivaroxaban; Telangiectasia, Hereditary Hemorrhagic; Venous Thrombosis

A 46-year-old man with antiphospholipid syndrome (APS) and previous pulmonary embolism on anticoagulation with rivaroxaban was brought in to the hospital after a syncopal episode. He was found to be hypotensive and tachycardic and later admitted to the intensive care unit. Clinical presentation and laboratory findings were consistent with adrenal insufficiency. MRI revealed bilateral adrenal haemorrhage and he received appropriate steroid replacement therapy. Symptoms slowly subsided and anticoagulation regimen was changed to warfarin. Adrenal haemorrhage was likely caused by APS and rivaroxaban, which brings into question whether novel oral anticoagulants are safe in this patient population.

Topics: Adrenal Gland Diseases; Adrenal Insufficiency; Anticoagulants; Antiphospholipid Syndrome; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Warfarin

The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and the assessment of the risk-to-benefit ratio of prolonged anticoagulation for patients with pulmonary embolism (PE).Anticoagulation is performed with unfractionated heparin (UFH) in hemodynamically unstable patients and with low molecular weight heparins (LWMH) or fondaparinux in normotensive patients. In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests. LMWH and fondaparinux are preferred over UFH in the initial anticoagulation of PE since they are associated with a lower risk of bleeding.All patients with PE require therapeutic anticoagulation for at least three months. The current 2019 guidelines of the European Society of Cardiology (ESC) recommend that all eligible patients should be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA). In patients with active cancer, Apixaban, Edoxaban and Rivaroxaban are effective alternatives to treatment with LMWH.The decision on the duration of anticoagulation should consider both, the individual risk of PE recurrence and the individual risk of bleeding. The risk for recurrent PE after discontinuation of treatment is related to the features of the index PE event. While patients with a strong transient risk factor have a low risk of recurrence and anticoagulation can be discontinued after three months, patients with strong persistent risk factor (such as active cancer) have a high risk of recurrence and thus should receive anticoagulant treatment of indefinite duration. Given the favourable safety profile of NOACs (especially if a reduced dosage of Apixaban or Rivaroxaban is initiated after at least six months of therapeutic anticoagulation), extended oral anticoagulation of indefinite duration should be considered for all patients with intermediate risk of recurrence.

Topics: Acute Disease; Dalteparin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fibrinolytic Agents; Fondaparinux; Guideline Adherence; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles

There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban.Methods and Results:In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events.. In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Neoplasms; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

To evaluate the short-term (12 weeks) safety and utilisation of rivaroxaban prescribed to new-user adult patients for the treatment of deep vein thrombosis and pulmonary embolism and for the prevention of recurrent deep vein thrombosis and pulmonary embolism in a secondary care setting in England and Wales.. An observational cohort study using the technique of Specialist Cohort Event Monitoring.. The Rivaroxaban Observational Safety Evaluation study was conducted across 87 participating National Health Service secondary care trusts in England and Wales.. 1532 patients treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism from September 2013 to January 2016.. Non-interventional postauthorisation safety study of rivaroxaban. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Risk of major bleeding in gastrointestinal, intracranial, and urogenital sites and (2) risk of all major and clinically relevant non-major bleeds.. Of a total of 4846 patients enrolled in the study from September 2013 to January 2016, 1532 were treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism. The median age of the deep vein thrombosis/pulmonary embolism cohort was 63 years, and 54.6% were men. The risk of major bleeding within the gastrointestinal, urogenital and intracranial primary sites was 0.7% (n=11), 0.3% (n=5) and 0.1% (n=1), respectively. The risk of major bleeding in all sites was 1.5% (n=23) at a rate of 8.3 events per 100 patient-years.. In terms of the primary outcome risk of major bleeding in gastrointestinal, intracranial and urogenital sites, the risk estimates in the population using rivaroxaban for deep vein thrombosis/pulmonary embolism were low (<1%) and consistent with the risk estimated from clinical trial data and in routine clinical practice.. ClinicalTrials.gov Registry (NCT01871194); ENCePP Registry (EUPAS3979).

Topics: Aged; Anticoagulants; Cohort Studies; England; Female; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Secondary Care; State Medicine; United Kingdom; Venous Thromboembolism; Venous Thrombosis; Wales

Topics: Aged; alpha-2-Antiplasmin; Blood Coagulation; Case-Control Studies; Factor Xa Inhibitors; Factor XIII; Female; Fibrin; Humans; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Time Factors; Treatment Outcome

The purpose of this meta-analysis is to compare the efficacy and safety of aspirin and rivaroxaban in the prevention of venous thromboembolism (VTE) following either total knee arthroplasty or total hip arthroplasty.. A comprehensive literature search of several electronic databases (PubMed, Embase, and Web of Science) was conducted to identify relevant studies. Outcomes of interest included VTE rate, deep vein thrombosis (DVT) rate, pulmonary embolism rate, major bleeding events, mortality rate, blood transfusion, and wound complication. Risk ratio (RR) with 95% confidence intervals (95%CIs) were calculated using a fixed-effects model or random-effects model.. A total of 8 studies with 97,677 patients met the inclusion criteria and were included in this meta-analysis. Compared with rivaroxaban, aspirin had a significantly higher incidence of DVT (RR = 1.48, 95%CI: 1.27, 1.72; P < .001), and decreased risk of blood transfusion (RR = 0.94, 95%CI: 0.93, 0.94; P < .001). However, there were no significant differences between the 2 drugs in terms of total VTE rate (RR = 1.39%, 95%CI: 0.94, 2.05; P = .101), pulmonary embolism rate (RR = 1.64, 95%CI: 0.92, 2.92; P = .094), mortality rate (RR = 1.13, 95%CI: 0.15, 8.27; P = .907), major bleeding (RR = 1.00, 95%CI: 0.44, 2.27; P = .995), and wound complication rate (RR = 0.37, 95%CI: 0.07, 1.87; P = .229).. Our results suggested that aspirin and rivaroxaban offered similar effect in the prevention of VTE after total knee arthroplasty or total hip arthroplasty. However, rivaroxaban seemed to have better effect than aspirin in reducing the risk of DVT, and aspirin was safer than rivaroxaban in decreasing the blood transfusion rate.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Blood Transfusion; Hemorrhage; Humans; Meta-Analysis as Topic; Pulmonary Embolism; Research Design; Rivaroxaban; Surgical Wound Infection; Systematic Review as Topic; Venous Thromboembolism; Venous Thrombosis

A morbidly obese patient with history of deep vein thrombosis and pulmonary embolism was diagnosed with an acute left upper extremity deep vein thrombosis and started on rivaroxaban. Three months later, the patient returned with swelling in the right arm and was found to have a right brachial thrombosis. Anticoagulant therapy was switched to a low-molecular-weight heparin, and patient was discharged on enoxaparin along with an order to follow-up with a hematologist. Subanalyses from randomized controlled trials, pharmacokinetic/pharmacodynamic, and real-world studies suggest that rivaroxaban may be effective and safe in morbidly obese patients for primary and secondary prevention of venous thromboembolism. However, the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis does not recommend the use of direct-acting oral anticoagulants in this population. If used, drug levels should be monitored to guide the therapy. Due to the disparity in data to show efficacy and safety of rivaroxaban in morbidly obese subjects, the interpatient variability of rivaroxaban's effects in subjects, and the lack of defined therapeutic range for rivaroxaban drug concentration, rivaroxaban should be used cautiously in this population.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Obesity, Morbid; Pulmonary Embolism; Rivaroxaban; Upper Extremity Deep Vein Thrombosis; Venous Thromboembolism

Topics: Aftercare; Anticoagulants; Benzamides; Duration of Therapy; Enoxaparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Length of Stay; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Ambulatory Care; Factor Xa Inhibitors; Humans; Outpatients; Patient Discharge; Pulmonary Embolism; Rivaroxaban

Paradoxical peripheral embolism and submassive pulmonary embolism (PE), secondary to cancer-associated thrombosis, are yet to be reported in the literature. Here we describe a case presenting with an acute peripheral arterial embolism. Subsequent testing revealed a PE and an intrahepatic cholangiocarcinoma as the likely risk factors for thrombus, with arterial spread likely achieved through a patent foramen ovale. The patient's symptoms almost relieved upon catheter-directed thrombus fragmentation and aspiration, catheter-directed thrombolysis, and combined anticoagulation. Embolism and major bleeding did not occur during 6 months of follow-up under systemic anticoagulation with rivaroxaban. This case documents that catheter-directed thrombolysis and anticoagulation could be likely effective and safe in the treatment and prevention of recurrence of paradoxical embolism and PE secondary to cancer-associated thrombosis.

Topics: Bile Duct Neoplasms; Cholangiocarcinoma; Embolism, Paradoxical; Factor Xa Inhibitors; Female; Humans; Middle Aged; Pulmonary Embolism; Rivaroxaban; Thrombolytic Therapy; Thrombosis; Treatment Outcome

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT.. To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK.. Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin.. Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Epistaxis; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Telangiectasia, Hereditary Hemorrhagic; Venous Thromboembolism; Warfarin

Topics: Angiography; Factor Xa Inhibitors; Humans; Patient Discharge; Pulmonary Embolism; Rivaroxaban; Ventricular Dysfunction, Right

Topics: Angiography; Factor Xa Inhibitors; Humans; Patient Discharge; Pulmonary Embolism; Rivaroxaban; Ventricular Dysfunction, Right

The objective was to determine whether a protocol combining risk stratification, treatment with the direct-acting oral anticoagulant rivaroxaban, and defined follow-up is associated with a greater proportion of patients with venous thromboembolism (VTE) treated as outpatients, without hospital admission.. We performed a multicenter study of patients diagnosed with VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) in two urban EDs, 18 months before and 18 months after implementation of an outpatient VTE treatment protocol. Patients with radiographically confirmed acute VTE were eligible. Our primary outcome was the proportion of VTE patients discharged from the ED or observation unit (i.e., without hospital admission). We performed subgroup analyses according to hospital, DVT and PE, and low-risk PE. We also assessed 7- and 30-day mortality, major bleeding, and returns to the ED. We compared proportions using chi-square and Fisher's exact tests.. We enrolled 2,212 patients, 1,081 (49%) before protocol and 1,131 (51%) after protocol. Mean age (59 years vs. 60 years), female sex (49% vs. 49%), other demographics, comorbid illness, and PE risk stratification were similar before and after. After protocol, more VTE (35% from 26%, p < 0.001), PE (18% from 12%, p = 0.002), low-risk PE (28% from 18%, p < 0.001), and DVT (60% from 49%, p = 0.002) patients were treated as outpatients. Mortality, bleeding, and returns to ED were rare and did not increase after protocol.. A treatment protocol combining risk-stratification, rivaroxaban treatment and defined follow-up is associated with an increase in PE and DVT patients treated as outpatients, with no increase in adverse outcomes.

Topics: Adult; Aged; Clinical Protocols; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Outpatients; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Venous Thrombosis

The non-interventional XALIA study compared the safety and effectiveness of rivaroxaban with standard anticoagulation for the treatment of venous thromboembolism in routine clinical practice. This substudy assessed the effect of treatment with rivaroxaban on healthcare resource use, hospital length of stay (LOS) and frequency of hospitalisation.. In XALIA, patients aged ≥18 years scheduled to receive ≥3 months of rivaroxaban or standard anticoagulation treatment for deep vein thrombosis (DVT) were eligible. Treatment decisions were at the physician's discretion. Healthcare resource use, including hospital admission for the index DVT and initial LOS, was documented. The main analyses in this substudy were conducted in a 1:1 propensity score-matched set (PMS) of patients, with adjustment for cancer at baseline.. In the PMS analysis, 1124 rivaroxaban-treated patients and 1124 standard anticoagulation-treated patients were included. Baseline characteristics were similar between groups (mean age 60.8 years vs. 61.2 years, DVT only rates of 89.7% vs. 90.2% and cancer rates of 8.4% vs. 8.5%, respectively). Of these, 433/1124 (38.5%) rivaroxaban-treated patients and 438/1124 (39.0%) standard anticoagulation-treated patients were hospitalised. Index event LOS in the PMS analysis was a least-squares mean of 2.6 days shorter with rivaroxaban vs. standard anticoagulation (5.4 vs. 8.0 days; geometric means ratio = 0.67 [95% confidence interval 0.61-0.74, P < 0.001]).. In XALIA, hospital LOS was shorter with rivaroxaban than with standard anticoagulation, consistent with the phase III study results. DVT treatment with rivaroxaban in routine clinical practice may reduce the cost per patient vs. standard anticoagulation.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Europe; Female; Health Resources; Humans; Length of Stay; Male; Middle Aged; Patient Readmission; Propensity Score; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Severe life-threatening thromboembolism may be caused exclusively by the presence of an acute CMV infection or due to the association of this agent and other thrombogenic factors. We report a case of an immunocompetent young female patient who presented a pulmonary embolism associated with acute CMV infection. The patient did not have any other apparent cause of thrombosis. She was successfully treated with rivaroxaban for 6 months without further episodes. To the best of our knowledge, this is the first report of a pulmonary embolism associated with CMV treated with a direct oral anticoagulant. The current case report calls attention to the importance of signs and symptoms of thromboembolism among patients with CMV. Direct oral anticoagulants can potentially bring the same benefits to treat pulmonary embolism associated with CMV as those observed in patients not infected.

Topics: Cytomegalovirus Infections; Factor Xa Inhibitors; Female; Humans; Pulmonary Embolism; Rivaroxaban

The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice.. This retrospective cohort study used linked administrative data. The study population (n = 14 577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015. Multivariate Cox proportional hazard models were used to estimate hazard ratios of thromboembolic events, mortality and bleeding events.. No differences between the DOACs were observed with regard to the risk of stroke, systemic embolism or cardiovascular death. In contrast, the risk of myocardial infarction was higher among patients prescribed apixaban in comparison to those on rivaroxaban (HR 1.67, 95% CI 1.02-2.71), and all-cause mortality was higher among rivaroxaban patients in contrast to both apixaban (1.22 [1.01-1.47]) and dabigatran (1.55 [1.16-2.05]) patients; rivaroxaban patients also had a higher risk of pulmonary embolism than apixaban patients (5.27 [1.79-15.53]). The risk of other major bleeds was higher among rivaroxaban patients compared to apixaban (1.50 [1.10-2.03]) and dabigatran (1.58 [1.01-2.48]) patients; the risks of gastrointestinal bleeds and overall bleeding were higher among rivaroxaban patients than among apixaban patients (1.48 [1.01-2.16] and 1.52 [1.21-1.92], respectively).. All DOACs were similarly effective in preventing strokes and systemic embolisms, while patients being treated with rivaroxaban exhibited the highest bleeding risks. Observed differences in the risks of all-cause mortality, myocardial infarction and pulmonary embolism warrant further research.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Scotland; Stroke; Treatment Outcome

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thromboembolic events including venous thromboembolism (VTE) in association with the presence of antiphospholipid antibodies. The standard treatment of VTE historically consists of anticoagulation therapy with warfarin, a vitamin K antagonist. Recently, direct oral anticoagulants, including rivaroxaban have become available for the treatment of VTE. However, the choice of anticoagulant, and the duration of anticoagulation in patients with APS has not been determined yet due to lack of evidence. Here, we report a case of recurrent venous thrombosis after discontinuation of rivaroxaban therapy and avoiding sedentary lifestyle in a patient with APS. We suggest that indefinite anticoagulation therapy might be needed even in low-risk APS cases.

Topics: Aftercare; Antiphospholipid Syndrome; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Rivaroxaban; Tomography, X-Ray Computed; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The clinical profile, evolution and complications of treatment with rivaroxaban in a cohort of patients presenting with venous thromboembolism (VTE) were analyzed in an observational, non-interventional and prospective study.A total of 111 patients were included in the study. Clinical data were collected from the medical history of the patients and recorded in a specific database.Mean age was 63.8 ± 17.4 years, 53.2% of patients were men, 55.9% had at least another concomitant condition, and 40.9% at least 1 VTE risk factor. 54.1% of patients presented with deep venous thrombosis, 32.4% with pulmonary embolism and 13.5% with both conditions simultaneously. The 61% of patients were admitted to hospital and mean hospital length-of-stay was 8.8 ± 9.9 days. After a mean follow-up 530 ± 464 days (median follow-up of 405 days), 3.9% of patients died and VTE recurrence occurred in 2.9% of patients. While receiving rivaroxaban, a first bleeding complication occurred in 8.1%; all events were minor bleeding.Our study supports the current literature data and confirms the similar results of real-life VTE patients with those enrolled in the rivaroxaban pivotal clinical trials. Rivaroxaban may facilitate outpatient treatment and might be considered as a first-line therapy for the management of VTE patients.

Topics: Aged; Factor Xa Inhibitors; Female; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Topics: Diagnosis, Differential; Factor Xa Inhibitors; Humans; Internal Medicine; Physicians; Pulmonary Embolism; Rivaroxaban; Tomography, X-Ray Computed

This study evaluated the trends in anticoagulation use after total hip arthroplasty (THA), and the effectiveness and safety of rivaroxaban compared to warfarin.. This retrospective database analysis used healthcare claims from the Truven Health MarketScan database (2010-2015). Patients undergoing elective THA were followed for use of anticoagulants after surgery. Logistic regression models were used to compare differences in deep vein thrombosis (DVT), pulmonary embolism (PE), and adverse events, within 90 days after THA, among warfarin and rivaroxaban users. Inverse probability treatment weighting was used to account for selection bias.. There were 12,876 users of warfarin and 10,892 users of rivaroxaban in commercially insured (CI) patients, and 7416 warfarin users and 4739 rivaroxaban users in Medicare supplement (MS) patients. Warfarin use decreased over time in both insurance cohorts, whereas rivaroxaban use increased from 2011 to 2015. Warfarin users were significantly more likely to experience both DVT (CI: odds ratio [OR] 2.63, 95% confidence interval 1.97-3.50; MS: OR 1.78, 95% confidence interval 1.38-2.29) and PE (CI: OR 2.60, 95% confidence interval 2.04-3.31; MS: OR 2.09, 95% confidence interval 1.66-2.65). There was no significant difference in rates of bleeding between the 2 agents, but warfarin users had higher odds of periprosthetic joint infection in both cohorts (CI: OR 1.57, 95% confidence interval 1.16-2.13; MS: OR 1.79, 95% confidence interval 1.14-2.81).. There has been an increase in prophylaxis with rivaroxaban, and a decrease in warfarin use after elective THA over 4 years. Warfarin users were more likely to experience DVT and PE than rivaroxaban, and bleeding risks were similar.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Databases, Factual; Female; Health Services; Hemorrhage; Humans; Male; Medicare; Middle Aged; Odds Ratio; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; United States; Venous Thrombosis; Warfarin

Topics: Aged; Cardiac Catheterization; Computed Tomography Angiography; Factor Xa Inhibitors; Humans; Male; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis

Rivaroxaban has numerous advantages over traditional anticoagulation therapy. Fixed doses can be administered without requiring routine monitoring of coagulation, and anticoagulation efficacy is more predictable. Safety, including fewer drug interactions, and reduced bleeding, is also improved with rivaroxaban based on current recommendations. The goal of this report was to explore if low-dose rivaroxaban 10 mg once daily was effective in an elderly patient who developed minor bleeding when treated with rivaroxaban (10 mg twice daily) for a pulmonary embolism.. We present an 88-year-old female with dyspnea and fatigue, which became increasingly worse over a month in the absence of medication. Her weight was 64 kg. Routine coagulation assays and renal function were normal at time of admission.. Deep vein thrombosis and pulmonary embolism were confirmed by venous compression ultrasonography and computed tomography pulmonary angiography.. Oral rivaroxaban 10 mg twice daily was administered, but the patient developed hemoptysis and gum bleeding 5 days later. The dose of rivaroxaban was reduced to 10 mg once daily, and bleeding gradually disappeared after 3 days.. At follow-up 90 days after treatment, the patient reported no discomfort. Venous compression ultrasonography and computed tomography pulmonary angiography showed normal results; therefore, treatment was terminated.. Elderly patients exhibit variable tolerance of anticoagulants, warranting careful consideration of the risk of bleeding. Low-dose rivaroxaban was an effective treatment for pulmonary embolism in the elderly patient presented here.

Topics: Administration, Oral; Aftercare; Aged, 80 and over; Computed Tomography Angiography; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Ultrasonography; Venous Thrombosis

Topics: Aged; Factor Xa Inhibitors; Humans; Lung; Male; Predictive Value of Tests; Pulmonary Embolism; Rivaroxaban; Thrombolytic Therapy; Tomography, X-Ray Computed; Treatment Outcome

The purpose of this study was to evaluate the efficacy and safety of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE).We performed a retrospective chart review of cancer patients with a pulmonary embolism, deep vein thrombosis, or both. Our analysis included all patients who received rivaroxaban from March 2013 to June 2016 at the Hemato-Oncology Division at the Pusan National University Hospital in Korea.Preliminary results identified 123 patients with a history of cancer that were treated with rivaroxaban. The average duration of rivaroxaban therapy was 95.25 days. While 35 patients had resolved VTE after the initiation of rivaroxaban, only one patient had it recur on rivaroxaban treatment. Major bleeding was observed in 6 (4.9%) patients and minor bleeding in 12 (9.8%) patients. The majority of bleeding events occurred spontaneously and most incidences of bleeding could be treated conservatively. Recurrence and major bleeding events on rivaroxaban were relatively low despite the fact that many patients had metastatic disease. Among 52 patient deaths (42.3%), none were due to VTE or bleeding complications; the cause of death in the majority of cases was cancer progression.Rivaroxaban is effective and safe for the treatment of cancer-associated VTE.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Republic of Korea; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Young Adult

This case series presents 3 patients with acute kidney injury taking apixaban or rivaroxaban and transitioning to a heparin infusion.. Case 1 was a 78-year-old man admitted with respiratory failure, acute decompensated heart failure, and acute kidney injury. He was taking apixaban for atrial flutter. He was transitioned to an i.v. heparin infusion and had 2 consecutive heparin antifactor-Xa levels greater than 2 units/mL. Heparin was held and resumed about 36 hours later when the apixaban anti-Xa level was less than 50 ng/mL. Case 2 was a 55-year-old man admitted with acute kidney injury, taking apixaban for a recent deep vein thrombosis. Apixaban anti-Xa levels were monitored and i.v. heparin was initiated when the level was less than 100 ng/mL, about 56 hours after the last apixaban dose. Case 3 was a 64-year-old woman admitted with sepsis and acute kidney injury taking rivaroxaban for pulmonary embolism, which occurred 2 weeks prior to admission. Rivaroxaban anti-Xa levels were monitored and i.v. heparin was initiated about 36 hours after the last dose when the level was less than 100 ng/mL. The management strategy did not lead to any thrombotic outcomes; however, 1 patient experienced bleeding.. Specific anti-Xa levels for rivaroxaban and apixaban appeared to be helpful in the transition of 3 patients to unfractionated heparin infusions in the setting of acute kidney injury. These levels provided enhanced, individualized care and likely helped avoid over and under anticoagulation.

Topics: Acute Kidney Injury; Administration, Oral; Aged; Atrial Flutter; Drug Monitoring; Drug Substitution; Factor Xa Inhibitors; Female; Heparin; Humans; Infusions, Intravenous; Kidney; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Renal Elimination; Rivaroxaban; Venous Thrombosis

: Thrombelastography (TEG) parameters and prothrombin time (PT), activated partial thromboplastin time (APTT) are compared and analysed. According to change of TEG parameters and assessment of haemostatic state of each patient, we try to explore the feasibility of individualized anticoagulant therapies. 87 people with hip or knee diseases awaiting arthroplasty were recruited. Haemoglobin levels and TEG parameters including R, K, α-angle, maximum amplitude, coagulation index were assessed in perioperative period. PT and APTT were assessed preoperatively. For 65 patients with normal TEG parameters, PT and APTT, we use tranexamic acid (TXA) to reduce blood loss during operation. As hypercoagulability group, 12 patients awaiting unilateral total knee arthroplasty with hypercoagulable state assessed by TEG parameters or risks for venous thromboembolism received daily 10-mg rivaroxaban until 24 h preoperatively and did not receive TXA during operation. All patients received intravenous administration of argatroban after 8 h postoperatively until day 3 and oral administration of rivaroxaban (10 mg) subsequently to prevent deep vein thrombosis or/and pulmonary embolism until 35 days postoperatively. TEG parameters have significant relationships with fibrinogen, platelet and APTT. The number of patients with abnormal haemostatic state assessed by TEG parameters is higher than that assessed by PT, APTT. TEG show hypercoagulability develops throughout perioperative period. There was no significant difference in haemoglobin concentration between hypercoagulability group and normal group in patients receiving unilateral total knee arthroplasty. TEG have higher sensitivity of perioperative abnormal haemostatic state than PT, APTT in primary arthroplasty. For patients with hypercoagulability, individualized anticoagulant therapies such as preoperative administration of rivaroxaban and not using TXA in operation is safe and effective.

Topics: Anticoagulants; Arginine; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Humans; Male; Middle Aged; Partial Thromboplastin Time; Perioperative Care; Pipecolic Acids; Postoperative Care; Preoperative Care; Prospective Studies; Prothrombin Time; Pulmonary Embolism; Rivaroxaban; Sulfonamides; Thrombelastography; Thrombophilia; Venous Thrombosis

BACKGROUND Renal vein thrombosis is uncommon and can be associated with nephrotic syndrome. It is associated with high patient morbidity , and it may lead to thromboembolic event. CASE REPORT A 44-year-old woman presented with shortness of breath, chest pain and tightness, due to bilateral pulmonary embolism originating from right renal vein thrombosis. The diagnosis was made by transthoracic echocardiography and enhanced computed tomography (CT) scan of chest, abdomen, and pelvis. No underlying diseases were found. She was treated with heparin infusion therapy and rivaroxaban with good clinical outcome. CONCLUSIONS A rare case is presented of isolated unilateral right renal vein thrombosis diagnosed following bilateral pulmonary embolism in a previously healthy 44-year-old woman, which was successfully treated with the DOAC, rivaroxaban.

Topics: Adult; Anticoagulants; Chest Pain; Dyspnea; Female; Humans; Pulmonary Embolism; Renal Veins; Rivaroxaban; Tomography, X-Ray Computed; Venous Thrombosis

Two large randomized controlled trials examined the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE). The aim of this epidemiological study was to analyze a cohort of Italian patients affected by VTE who were treated with rivaroxaban in clinical practice. The data were collected by physicians using an online electronic questionnaire. The study was performed during a 6-month period from January to June 2014. We analyzed the clinical characteristics, risk factors for VTE, comorbidities, diagnostic techniques, and treatments in the whole population and in the subgroups with deep vein thrombosis (DVT) only, pulmonary embolism (PE) only, and DVT+PE. Overall, 75.9% of patients were affected by DVT; 20% of patients had DVT and PE; and 4.8% of patients had only PE. Approximately 90% of patients were symptomatic upon diagnosis, and 46.3% of patients required hospitalization. More than half of the patients switched to rivaroxaban after receiving another anticoagulant therapy. The main reasons for changing treatment included difficulties in managing vitamin K antagonists, patient choice, and prothrombin time-international normalized ratio (PT-INR) instability. The switch to rivaroxaban occurred after a mean of 1.8 PT-INR measurements. Clinical characteristic were overall similar to those of patients enrolled in prior clinical trials evaluating the safety and efficacy of rivaroxaban.

Topics: Adult; Aged; Anticoagulants; Disease Management; Drug Substitution; Humans; International Normalized Ratio; Italy; Middle Aged; Pulmonary Embolism; Risk Factors; Rivaroxaban; Surveys and Questionnaires; Venous Thromboembolism

Since 2010, four oral anticoagulants have been approved for marketing in addition to warfarin for treatment of thromboembolic disease. Limited head-to-head data exist comparing these treatments, leaving patients and clinicians with little guidance for selecting a strategy that balances recurrence reduction with bleeding risk. In the dabigatran, apixaban, rivaroxban, edoxaban and warfarin comparative effectiveness research study, we compare all five currently available oral anticoagulant agents for the extended treatment of deep venous thrombosis and pulmonary embolism, as well as no extended treatment, and evaluate whether results differ in specific sub-populations. As our population includes Medicare novel anticoagulant users and large numbers of commercially insured and Medicaid patients, our results will likely be transportable to the majority of US patients experiencing a DVT or pulmonary embolism.. NCT03271450.

Topics: Anticoagulants; Antithrombins; Comparative Effectiveness Research; Dabigatran; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Research Design; Rivaroxaban; Thiazoles; Venous Thrombosis; Warfarin

The incidence of venous thromboembolism (VTE) is lower in Asian populations than in Western populations. The objective of the present study was to evaluate the annual age- and sex-adjusted incidence (ASR) of VTE from 2009 to 2013 in South Korea. In addition, annual change in the pattern of VTE treatment during the study period was estimated because a new direct oral anticoagulant (DOAC) had become available and was covered by health insurance in Korea beginning in January 2013. VTE cases from 2009 to 2013 were retrospectively identified based on both diagnostic and medication codes of anticoagulants used for initial treatment using the Korean Health Insurance Review and Assessment Service (HIRA) databases. The incidence of VTE increased yearly. It was significantly higher in the older population than in the younger population, and it was higher in females than in males. In 2009, ASRs of VTE, deep vein thrombosis, and pulmonary embolism were 21.3, 8.1, and 13.2 cases per 100,000 individuals, respectively in 2009. These increased to 29.2, 12.7, and 16.6 cases per 100,000, respectively, in 2013. Prescription rates of warfarin and low-molecular-weight heparin decreased with the introduction of a new anticoagulant in 2013. The proportion of subjects who underwent mechanical procedures decreased annually. The ASR of VTE in Korea continuously increased from 2009 to 2013, reflecting an increased awareness and detection of VTE as well as improved survival of patients with cancer and other morbidities. Following its introduction, DOAC rapidly replaced other anticoagulants for the treatment of VTE.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Pulmonary Embolism; Republic of Korea; Retrospective Studies; Rivaroxaban; Sex Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin; Young Adult

Topics: Anticoagulants; Antithrombins; Clinical Trials as Topic; Dabigatran; Hemorrhage; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Survival Analysis; Venous Thrombosis; Warfarin

A 71-year-old female with a history of pulmonary embolism treated with rivaroxaban presented with acute onset shortness of breath, chest pain and palpitations. Computed tomographic pulmonary angiography (CTPA) revealed multiple bilateral pulmonary emboli. The patient was concurrently prescribed carbamazepine and was later diagnosed with recurrence of breast cancer during the admission. We discuss common drug interactions pertinent to direct oral anticoagulants (DOACs) that can increase the risk of further venous thromboembolism. This case report highlights the importance of reviewing patient medications when considering anticoagulants and the need to raise awareness of these drug interactions among clinicians when making their choice of anticoagulation. It also reinforces the current lack of evidence for use of DOACs in patients with solid organ malignancies.

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation; Breast Neoplasms; Carbamazepine; Computed Tomography Angiography; Diagnosis, Differential; Drug Interactions; Female; Humans; Medication Therapy Management; Pulmonary Artery; Pulmonary Embolism; Rivaroxaban

We report an unusual presentation of pulmonary embolism (PE) where a 58-year-old man first developed symptoms of community-acquired pneumonia. Despite antibiotic therapy, he remained unwell with rising inflammatory markers, general malaise and persistent cough. He developed stony dull percussion and absent breath sounds to his left mid to lower zones. Serial chest x-rays showed progression from lobar consolidation to a large loculated left-sided pleural collection. CT chest showed left-sided lung abscess, empyema and bronchopleural fistulation. Incidentally, the scan revealed acute left-sided PE and its distribution corresponded with the location of the left lung abscess and empyema. The sequence of events likely started with PE leading to infarction, cavitation, abscess formation and bronchopleural fistulation. This patient was managed with a 6-month course of rivaroxaban. After completing 2 weeks of intravenous meropenem, he was converted to 4-week course of oral co-amoxiclav and metronidazole and attained full recovery.

Topics: Abscess; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchial Fistula; Disease Progression; Drug Therapy, Combination; Humans; Infarction; Male; Meropenem; Metronidazole; Middle Aged; Pleural Diseases; Pneumonia; Pulmonary Embolism; Radiography, Thoracic; Rivaroxaban; Thienamycins; Treatment Outcome

Topics: Biopsy; Drug Substitution; Factor Xa Inhibitors; Glomerulonephritis, IGA; Humans; IgA Vasculitis; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thrombosis

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.

Topics: Biomarkers; Consensus; Disease Management; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Interdisciplinary Communication; Italy; Patient Care Team; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Ultrasonography; Venous Thrombosis

Topics: Computed Tomography Angiography; Echocardiography; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Diseases; Humans; Male; Middle Aged; Predictive Value of Tests; Pulmonary Embolism; Recombinant Proteins; Rivaroxaban; Thromboembolism; Thrombolytic Therapy; Tissue Plasminogen Activator

Venous thromboembolism may result from prolong immobilization following intracerebral hemorrhage. Massive pulmonary embolism with associated right heart failure is life-threatening, requiring treatment with anticoagulants or even thrombolytic agents. However, these drugs are contraindicated after a recent hemorrhagic episode, as they may induce further hemorrhage. There are no guidelines for treatment in these circumstances.. A 57-year-old man experienced massive pulmonary embolism and shock 18 days after an intracerebral hemorrhage.. Tachycardia and high D-dimer (21.27 mg/L fibrinogen-equivalent units) were noted. Chest computed tomography showed bilateral pulmonary trunk embolism.. Heparinization were used and activated partial thromboplastin time therapeutic range was 50 to 70 seconds. Fortunately, shock status and shortness of breath improved two days later. Continuing high dose Rivaroxaban was administrated for three weeks.. There was no recurrent intracranial hemorrhage (ICH) following treatment for three-weeks with high-dose and one-year with standard dose of rivaroxaban. This report presents a treatment option in the management of these difficult clinical situations.. The combination of unfractionated heparin infusion and continuing non-Vitamin K antagonist oral anticoagulants use could manage life-threatening pulmonary embolism following recent ICH. Theoretically, the use of NOAC is a safer strategy if the patient with previous history of major ICH.

Topics: Dose-Response Relationship, Drug; Drug Therapy, Combination; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Intracranial Hemorrhages; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Shock; Tachycardia; Tomography, X-Ray Computed

Massive pulmonary embolism (PE) is defined by acute PE with sustained systemic arterial hypotension that is below 90 mm Hg for at least 15 min or requires inotropic agents (Jaff et al., 2011). For patients with absolute contraindications to thrombolysis, interventional treatment requires the removal of obstructing thrombi from the main pulmonary arteries to facilitate RV recovery and improve symptoms and survival (European Respiratory Society et al., 2014). For patients with acute PE, anticoagulation is recommended, with the objective of preventing both early death and recurrent symptomatic or fatal VTE. Rivaroxaban, an oral factor Xa inhibitor and a new oral anticoagulants, shows effective anticoagulation within hours of administration. It has a fixed-dose regimen, and requires no laboratory monitoring (EINSTEIN-PE Investigators et al., 2012). However, the efficacy and safety of rivaroxaban plus catheter-directed treatment for massive PE and bleeding is unknown. This case demonstrated that a combination of catheter-directed treatment and rivaroxaban was safe and effective in for the treatment of severe PE with vaginal bleeding.

Topics: Administration, Oral; Catheterization; Computed Tomography Angiography; Electrocardiography; Factor Xa Inhibitors; Female; Heparin; Humans; Infusions, Intravenous; Middle Aged; Pulmonary Embolism; Rivaroxaban; Tachycardia; Thrombolytic Therapy; Treatment Outcome; Uterine Hemorrhage

Topics: Anticoagulants; Carbamazepine; Humans; Obesity; Pulmonary Embolism; Rivaroxaban

Rivaroxaban, a factor Xa inhibitor used as a direct oral anticoagulant, is beneficial over warfarin in terms of food-drug interactions and the need for therapeutic monitoring in patients with acute venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Because there is little data regarding VTE treatment in Japan, a real-world survey of Japanese patients being treated with rivaroxaban for VTE is needed.. The Japanese Registry of Rivaroxaban Effectiveness & Safety for the Prevention of Recurrence in Patients with Deep Vein Thrombosis and Pulmonary Embolism has been established to investigate the clinical outcomes of rivaroxaban for the initial treatment and prevention of symptomatic recurrent VTE in Japanese patients with acute symptomatic/asymptomatic VTE. 150 institutions in Japan will enrol patients in the study; the target enrolment is 1000. All patients will be followed up two times a year for at least 18 months and up to 3 years after their enrolment. The primary outcome is symptomatic recurrent VTE occurring during the study period. The principal safety outcome is clinically relevant bleeding (ie, major bleeding or clinically relevant non-major bleeding) occurring during treatment. A clinical events committee will adjudicate all outcomes.. The study protocol has been approved by the Nihon University Itabashi Hospital, Clinical Research Ethics Committee and all local institutional ethics committees of the participating hospitals. Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals.. NCT03091621,UMIN000025072; Pre-results.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Japan; Male; Prospective Studies; Pulmonary Embolism; Recurrence; Registries; Research Design; Risk Factors; Rivaroxaban; Venous Thrombosis; Warfarin

There are numerous studies discussing thromboprophylaxis after total joint arthroplasty (TJA), with varying conclusions. Patient inclusion criteria may be different for each study, which may lead to selection bias and misrepresentation of data. This study aimed to investigate if industry funding impacted patient demographics and overall reported outcomes of studies analyzing venous thromboembolism (VTE) prevention after TJA.. Electronic searches were completed using Ovid, PubMed, and Embase databases. Studies were included if (1) they are published in the English language between 2000 and 2016; (2) they included patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA); and (3) they evaluated prevention and control of postoperative VTE with at least one of the following thromboprophylactic agents: aspirin, enoxaparin, dalteparin, dabigatran, apixaban, rivaroxaban, dabigatran, ximelagatran, fondaparinux, or coumadin. Data were extracted and analyzed via mixed-effect logistic regression.. Fifty-seven studies were included; 29 were industry funded, and 28, nonfunded. There were no significant differences between patient's age, body mass index, or revision exclusions between funded and nonfunded studies. Funded studies reported less pulmonary embolisms, fewer events of major bleeding, and significantly less 90-day mortality compared with nonfunded studies.. Industry-funded studies reported less pulmonary embolisms, major bleeding, and mortality compared with nonfunded studies. Detailed demographic data were missing from the literature, and we were unable to demonstrate the cause of different reported outcomes between industry-funded and nonfunded studies. Further investigations should be aimed toward understanding how funded studies report less adverse outcomes in analyzing VTE after TJA.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Conflict of Interest; Dabigatran; Enoxaparin; Female; Fondaparinux; Health Care Sector; Hemorrhage; Humans; Male; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Warfarin

Topics: Administration, Oral; Anticoagulants; Antithrombins; Dabigatran; Dalteparin; Factor Xa Inhibitors; Hemorrhage; Humans; Multicenter Studies as Topic; Neoplasms; Observational Studies as Topic; Patient Acceptance of Health Care; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Using data from the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN-CHOICE) trial, this study assessed cost impact of continued anticoagulation therapy with rivaroxaban vs aspirin.. Total health-care costs (2016 USD) associated with rivaroxaban and aspirin were calculated as the sum of clinical event costs and drug costs from a US managed care perspective. Clinical event costs were calculated by multiplying event rate by cost of care. One-year Kaplan-Meier clinical event rates for recurrent pulmonary embolism, recurrent DVT, all-cause mortality, and bleeding were obtained from EINSTEIN-CHOICE. Cost of care was determined by literature review. Drug costs were the product of drug price (wholesale acquisition cost) and treatment duration. A one-way sensitivity analysis was conducted.. Rivaroxaban users had lower per patient per month (PPPM) clinical event costs compared with aspirin users ($123, $243, and $381 for rivaroxaban 10 mg, rivaroxaban 20 mg, and aspirin, respectively). However, vs aspirin, PPPM total health-care costs were $24 higher for patients treated with rivaroxaban 10 mg ($143 higher for rivaroxaban 20 mg) due to higher cost of rivaroxaban. With a 15% discount for rivaroxaban 10 mg, the lower cost of clinical events for the rivaroxaban-treated patients more than fully offset the higher drug costs, and yielded a $19 lower total health-care cost.. Continued therapy with rivaroxaban 10 and 20 mg vs aspirin was associated with lower clinical event costs but higher total health-care costs; with a 15% drug discount rivaroxaban 10 mg had lower total health-care costs than aspirin.

Topics: Anticoagulants; Aspirin; Cost Savings; Dose-Response Relationship, Drug; Drug Monitoring; Female; Health Care Costs; Hemorrhage; Humans; Male; Middle Aged; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Venous Thromboembolism

Detection of new oral anticoagulant (NOAC) levels by screening, special and global tests, and liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) is important in clinical situations when the cause of bleeding needs to be determined.. We compared a routine coagulation test, special function test for NOACs, global coagulation test, and an LC-MS/MS method that enables simultaneous determination of apixaban, dabigatran and rivaroxaban in human plasma within one analysis to determine the optimal indication of the comparison methods, including their limitations and interferences.. This study was conducted on a set of blood samples from 116 patients treated with NOACs. The results of both specific dilute thrombin time (dTT) tests for dabigatran provided the same results as the activated partial thromboplastin time (aPTT) screening test in comparison with LC-MS/MS as a reference. The dTT assay HemosIL® showed better results for low concentrations when compared to LC-MS/MS than dTT HYPHEN® as HemosIL® uses a non-linear calibration curve. Results of the specific anti-Xa assay yielded better results than the prothrombin time test in comparison with LC-MS/MS as a reference, especially for apixaban, but also for rivaroxaban. Our LC MS/MS method is simply feasible, but only in a specialized laboratory. The method is easy-to-use for the simultaneous determination of all dabigatran, apixaban and rivaroxaban by LC-MS/MS within three minutes with a concentration range of 1 to 500 µg/L without dilution.. In the normal practice of the coagulation laboratory, it is advisable to use specific tests for NOAC determination as screening and global assays are not sufficiently specific. The dTT test is the optimal choice for dabigatran determination and for xabans to determine anti-Xa activity. The LC-MS/MS method is suitable as an arbitration method for serious conditions.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Chromatography, Liquid; Dabigatran; Factor Xa Inhibitors; Humans; Partial Thromboplastin Time; Prothrombin Time; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Tandem Mass Spectrometry; Thrombin; Venous Thrombosis

Patients with psychiatric disorders in critical condition are difficult to treat. In this study, we report on a patient with underlying schizoaffective disorder who developed catatonia, cardiac arrest, and pulmonary embolism, as well as a successful treatment strategy.. The inpatient is a 41-year-old morbidly obese male with schizoaffective disorder whose clozapine dosage was titrated from 100 mg to 175 mg due to auditory hallucination and agitation. The patient abruptly developed acute cardiopulmonary symptoms associated with an elevated troponin-I level. He was transferred to a cardiac intensive care unit, where he remained for 3 days. He was also found to have excited catatonic symptoms, and the lorazepam-diazepam protocol was initiated to quickly relieve the catatonia. Once the coronary angiogram was read as normal, the patient was transferred back to the psychiatric ward. However, the patient then suffered from in-hospital cardiac arrest. He was resuscitated and again transferred to the medical intensive care unit. Computed tomography confirmed the diagnosis of a pulmonary embolism. The patient was treated with Rivaroxaban 30 mg/d for the first 21 days, followed by 20 mg daily for 3 months. To control his severe and refractory psychotic symptoms, the patient was re-prescribed clozapine. During the 15-month follow-up period, the patient demonstrated a fair response and tolerability to clozapine 150 mg without symptoms relapse and no thromboembolic event.. This report can serve to remind psychiatrists and physicians to be aware of fatal conditions in patients with psychiatric diseases and physical illnesses.

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Drug Therapy, Combination; Factor Xa Inhibitors; Hallucinations; Humans; Male; Obesity, Morbid; Psychotic Disorders; Pulmonary Embolism; Rivaroxaban; Treatment Outcome

Acute compartment syndrome is a limb-threatening condition often associated with high-energy injury. We present the case of a man who sustained compartment syndrome secondary to an atraumatic tear in the gastrocnemius muscle and the complications which arose in his treatment due to his being on rivaroxaban.

Topics: Compartment Syndromes; Diagnosis, Differential; Factor Xa Inhibitors; Fasciotomy; Hemostatic Techniques; Humans; Male; Middle Aged; Muscle, Skeletal; Postoperative Hemorrhage; Pulmonary Embolism; Rivaroxaban

Background Direct oral anticoagulants (DOACs) demonstrate a lower risk-benefit ratio than vitamin K antagonists (VKAs) for secondary thromboprophylaxis of thrombotic events. But there are no data on the efficacy of DOACs for the prevention of thrombotic recurrence in patients with antiphospholipid syndrome (APS). In this study, we evaluated the efficacy of DOACs to prevent recurrences of thrombotic events in patients with APS. Methods This was a single-center pilot, using a multi-step Fleming design. If seven or fewer patients presented treatment failure with rivaroxaban, the study could conclude efficacy. Results A total of 23 patients were included. APS involved the veins only ( n = 19), arteries only ( n = 2) or both ( n = 1) and 1 patient exhibited catastrophic antiphospholipid syndrome (CAPS). Overall, two patients were positive for lupus anticoagulant, anti-beta-2 glycoprotein I antibodies and anticardiolipid antibodies (triple positivity). The mean duration of follow up was 35.6 (range, 29-40) months. A total of six treatment failures were reported: one patient, with triple positivity, developed bilateral distal pulmonary embolism (PE) after 20 months of treatment with rivaroxaban, two patients refused to take rivaroxaban, the treatment was stopped in three other patients: two with adverse effects and one with chronic iron-deficiency anemia. Conclusions Rivaroxaban may represent an alternative for secondary thromboprophylaxis for thrombo-embolism in patients with APS, in particular, those with poor international normalized ratio (INR) control and those who are not at the highest risk of recurrent thrombosis, such as those with triple positivity.

Topics: Administration, Oral; Adult; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Cohort Studies; Female; Follow-Up Studies; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Pilot Projects; Pulmonary Embolism; Rivaroxaban; Thrombosis; Young Adult

Deep vein thrombosis (DVT) and pulmonary embolism are collectively known as venous thromboembolism (VTE), which is a common vascular disease and a major cause of morbidity and mortality worldwide. We compare effectiveness and safety of rivaroxaban versus warfarin in a prospective cohort of routine care patients with incident unprovoked VTE.. In this propensity-matched cohort study, we linked nationwide Danish health registries to identify all patients with a first hospital diagnosis of unprovoked VTE who were new users of rivaroxaban or warfarin. Excluded patients included those who had not been residents in Denmark for at least 1 year before VTE diagnosis, patients with outpatient VTE diagnosis only, patients with other indications for oral anticoagulation treatment, patients with previous experience of oral anticoagulation, patients who did not have a prescription for rivaroxaban or warfarin within 7 days of VTE, and patients who redeemed prescriptions for both rivaroxaban and warfarin, or other oral anticoagulants. Primary effectiveness outcome was recurrent VTE and primary safety outcome was major bleeding. We used propensity matching and Cox regression to compare rates of the outcomes with rivaroxaban versus standard treatment.. From Dec 9, 2011, to Feb 28, 2016, we identified 29 963 patients with incident VTE. After exclusion, we identified 1734 propensity-matched patients given rivaroxaban (1751 before propensity matching) and 2945 propensity-matched patients given warfarin. The rate of recurrent VTE at 6 months' follow-up was 9·9 incidents per 100 person-years with rivaroxaban versus 13·1 incidents per 100 person-years with warfarin, yielding a hazard ratio (HR) of 0·74 (95% CI 0·56-0·96). The rate of major bleeding was 2·4 per 100 person-years at 6 months in rivaroxaban users versus 2·0 in warfarin users (HR 1·19, 95% CI 0·66-2·13).. In this clinical practice setting, rivaroxaban in patients with unprovoked VTE was associated with reduced risk of recurrent VTE compared with standard treatment, without compromising safety.. Obel Family Foundation.

Topics: Administration, Oral; Aged; Anticoagulants; Denmark; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Propensity Score; Prospective Studies; Pulmonary Embolism; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Antithrombins; Dabigatran; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Review Literature as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Aged; Anticoagulants; Drug Packaging; Factor Xa Inhibitors; Female; Humans; Medication Errors; Pulmonary Embolism; Rivaroxaban

Venous thromboembolism (VTE), comprising deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a major healthcare concern that results in substantial morbidity and mortality with great economic burden for healthcare systems. Hence, the need for effective and efficient treatment of patients with VTE is important for both clinical and economic reasons. The objective of this study was to evaluate the cost effectiveness of rivaroxaban compared to standard of care (SoC) with enoxaparin followed by dose-adjusted vitamin-K antagonists for the treatment of DVT and PE in Greece.. An existing Markov model was locally adapted from a third-party payer perspective to reflect the management and complications of DVT and PE in the course of 3-month cycles, up to death. The clinical inputs and utility values were extracted from published studies. Direct medical costs, obtained from local resources, were incorporated in the model and refer to year 2017. Both costs and outcomes were discounted at 3.5%. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was calculated. Probabilistic sensitivity analysis (PSA) was carried out to deal with uncertainty.. The base-case analysis showed that rivaroxaban in 3- and 6-month treatment duration for DVT and PE, respectively, as this is the common clinical practice in Greece, was associated with a 0.02 and 0.01 increment in QALYs compared to SoC, respectively. Rivaroxaban was associated with a reduced total cost in DVT (€85) but with an additional total cost in PE (€2) compared to SoC. Therefore, rivaroxaban was a dominant (less costly, more effective) and cost-effective (ICER: €177) alternative over SoC for the management of DVT and PE, respectively. PSA revealed that the probability of rivaroxaban being cost effective at a threshold of €34,000 per QALY gained was 99% and 81% for DVT and PE, respectively.. Rivaroxaban may represent a cost-effective option relative to SoC for the management of DVT and PE in Greece.

Topics: Aged; Anticoagulants; Cost-Benefit Analysis; Enoxaparin; Fibrinolytic Agents; Greece; Humans; Middle Aged; Pulmonary Embolism; Quality-Adjusted Life Years; Rivaroxaban; Venous Thrombosis

The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012-6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95 % confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19 % (95 %CI=10-27 %) reduction in recurrent VTE and a 21 % (95 %CI=4-35 %) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients' hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies.

Topics: Anticoagulants; Databases, Factual; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Pulmonary Embolism; Recurrence; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Due to limited evidence on the impact of rivaroxaban in clinical practice, we compared the effectiveness of rivaroxaban versus standard of care (SOC) among patients in the Veterans Health Administration.. Adult patients with continuous enrollment in a health plan with medical and pharmacy benefits for ≥12 months before and ≥3 months after an inpatient diagnosis of pulmonary embolism (PE) between October 1, 2011, and June 30, 2015, and a prescription claim for an anticoagulant during the index hospitalization, were included. SOC drugs were low-molecular-weight heparin, unfractionated heparin, and warfarin. Propensity score matching was used in comparing PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), hospital-acquired complications (HACs), health care resource utilization, and costs among patients receiving SOC versus rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HACs.. Among 6746 patients with PE, 208 received rivaroxaban, 4641 received SOC and 1897 received other anticoagulants. Most (95%) were male; 22% were black. After 1:3 propensity score matching, there were 203 rivaroxaban and 609 SOC patients. During the 90-day follow-up, rivaroxaban users had similar rates of PE-related outcomes, but fewer had experienced at least 1 HAC (10.3% vs 15.9%; P = 0.0506), resulting in better net clinical benefit (82.8% vs 71.1%; P = 0.001). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs 19.9; P = 0.0005), a similar rehospitalization rate (0.2 vs 0.3; P = 0.084), lesser inpatient costs (US $3501 vs $6189; P < 0.0001), lesser inpatient costs and lesser total costs ($10,545 vs $14,192; P = 0.0002). When the sample was limited to patients with low-risk PE, we found similar patterns.. Patients with PE prescribed rivaroxaban had similar PE-related outcomes, but fewer HACs and lesser total costs, than did patients on SOC.

Topics: Adolescent; Adult; Aged; Anticoagulants; Female; Health Care Costs; Hemorrhage; Heparin; Hospitalization; Humans; Inpatients; Male; Middle Aged; Propensity Score; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Veterans; Warfarin; Young Adult

Rivaroxaban is a novel oral anticoagulant indicated for prophylaxis against deep vein thrombosis and pulmonary embolism in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery.. To evaluate major bleeding (MB) in THR/TKR patients receiving post-operative rivaroxaban.. Electronic medical records of nearly 10 million US Department of Defense (DoD) beneficiaries were queried from 1 January 2013 through 30 June 2015. Using the validated Cunningham case-finding algorithm, post-surgical MB events in rivaroxaban users were identified and analyzed. The incidence of MB was determined, and descriptive statistics were used to compare patient characteristics and other covariates in those with and without MB. Two additional methods were used to explore and identify bleeding cases that were not considered MB events per the study case-finding algorithm.. A total of 12,429 patients received THR and/or TKR surgery, and were post-operatively prescribed rivaroxaban. Nine patients had MB, yielding an incidence proportion of 0.07% (95% CI 0.02-0.13). The alternative case-finding methods found bleeding incidences of 0.46% and 0.21%, though it is not clear whether these are clinical MB cases, since the alternative methods were not validated.. The incidence of MB in this retrospective analysis is lower than that observed in the clinical trials of rivaroxaban. Whether this is due to lower real-world MB rates or challenges with case-finding algorithms is unclear.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Electronic Health Records; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Venous Thrombosis

Topics: Adult; Anticoagulants; Electrocardiography; Factor Xa Inhibitors; Heparin; Humans; Male; Pulmonary Embolism; Rivaroxaban; Thrombocytopenia; Tomography, X-Ray Computed; Video Recording

Topics: Antithrombins; Blood Coagulation; Body Mass Index; Dabigatran; Drug Substitution; Humans; Male; Middle Aged; Obesity, Morbid; Pulmonary Embolism; Risk Factors; Rivaroxaban; Treatment Failure

Crohn's disease and ulcerative colitis are the two major types of inflammatory bowel disease, and affect mainly the gastrointestinal tract but also have extraintestinal sequelae, such as arterial and venous thromboembolism. Thromboembolic complications, particularly pulmonary thromboembolism, can be life threatening and require prompt management with anticoagulants. Conventional vitamin K antagonists have been used for the treatment of thromboembolic complications, but the development of novel oral anticoagulants has shifted the paradigm. We report a case of a 42-year-old female with ulcerative colitis who experienced an acute flare-up due to cytomegalovirus superinfection with pulmonary thromboembolism. She was treated with oral mesalamine, intravenous steroid and ganciclovir and low-molecular-weight heparin, followed by rivaroxaban, a novel oral anticoagulant. Her symptoms resolved after treatment, and no recurrence was noted during a 6-month post-treatment follow-up.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Colitis, Ulcerative; Colonoscopy; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Intestinal Mucosa; Mesalamine; Pulmonary Embolism; Rivaroxaban; Tomography, X-Ray Computed

Here, we present the case of a patient with the findings of an early intracardiac thrombus and a pulmonary embolus after major trauma. A large clot was identified extending from the inferior vena cava into the right atrium and ventricle in the setting of preserved right ventricular function. Post-traumatic intracardiac thrombus is extremely rare and no comparable cases have previously been described in the absence of a congenital heart defect and obvious myocardial injury. Best practice afterpost-traumatic intracardiac thrombus is not well established but we found that early inferior vena cava filter placement and treatment with therapeutic coagulation resulted in clinical improvement, resolution of the thrombus and no further emboli. The successful use of rivaroxaban, a direct-acting oral anticoagulant, to treat a right heart thrombus has, to our knowledge, not previously been reported. Early acute traumatic coagulopathy has received much attention but the hypercoagulable state that often follows is less well appreciated.

Topics: Echocardiography; Factor Xa Inhibitors; Female; Heart Atria; Heart Diseases; Humans; Pulmonary Embolism; Rare Diseases; Rivaroxaban; Thromboembolism; Thrombosis; Treatment Outcome; Vena Cava Filters; Vena Cava, Inferior; Wounds and Injuries; Young Adult

Topics: Administration, Oral; Amiodarone; Atrial Fibrillation; Drug Administration Schedule; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Parotid Gland; Perioperative Care; Phenprocoumon; Postoperative Complications; Pulmonary Embolism; Rivaroxaban

Anticoagulant-associated heavy menstrual bleeding (HMB) is an underrecognized but not uncommon problem in clinical practice. Premenopausal women should be advised of the potential effect of anticoagulant therapy on menstrual bleeding at the time of treatment initiation. Consequences of HMB should be assessed and treated on an ongoing basis. In the acute setting, the decision to withhold anticoagulants is based on an individual patient's risk of thrombosis and the severity of the bleeding. For women who require long-term anticoagulation, a levonorgestrel intrauterine system, tranexamic acid (during menstrual flow), high-dose progestin-only therapy, or combined hormonal contraceptives are effective for controlling HMB. The risk of thrombosis during anticoagulant therapy with these treatments is not well studied but is likely to be low. Selection of type of hormonal therapy is based on patient preference, other indications for and contraindications to therapy, adverse effect profile, and ongoing thrombotic risk factors. Women who do not respond to medical treatment or who do not wish to retain their fertility should be considered for surgical management.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Dose-Response Relationship, Drug; Female; Humans; Menorrhagia; Practice Guidelines as Topic; Pulmonary Embolism; Rivaroxaban; Tranexamic Acid; Treatment Outcome; Venous Thromboembolism; Young Adult

BACKGROUND Thrombophilia is a predisposition to thrombosis. Genetic causes include antithrombin III, protein C, protein S, factor V Leiden, prothrombin 20210A allele, and MTHFR mutations. Other genetic factors causing thrombosis and pulmonary embolism have been identified in recent studies, including 4G/4G polymorphism of the PAI-1 gene. CASE REPORT A patient with a personal and family history of recurrent thrombosis and pulmonary embolism was admitted to our Internal Medicine Department. After the most common acquired risk factors for thromboembolism were ruled out, the patient and her family members underwent genetic diagnostic testing. These tests showed homozygous 4G/4G polymorphism of the PAI-1 gene in 14 subjects, homozygous 4G/4G polymorphism of the PAI-1 gene and C677T/A1298C polymorphism of the MTHFR gene in 4 subjects, and heterozygous 4G/4G polymorphism of the PAI-1 gene and C677T/A1298C polymorphism of the MTHFR gene in 3 subjects. Afterwards, we initiated the administration of Rivaroxaban, with beneficial results. CONCLUSIONS No thrombotic recurrence has been observed in the patient since 2014. This case report shows the efficacy and superiority of Rivaroxaban over traditional anticoagulants in the treatment of hereditary thrombophilia. Further studies are clearly needed before Rivaroxaban can be recommended as a standard treatment in patients with inherited thrombophilia.

Topics: Factor Xa Inhibitors; Female; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Pulmonary Embolism; Rivaroxaban; Thrombophilia

Topics: Computed Tomography Angiography; Contraceptives, Oral, Combined; Factor Xa Inhibitors; Female; Humans; Pulmonary Embolism; Risk Factors; Rivaroxaban; Venous Thromboembolism; Young Adult

We sought to compare the length of stay (LOS) and total costs for patients with pulmonary embolism (PE) treated with either rivaroxaban or parenterally bridged warfarin.. This retrospective claims analysis was performed in the Premier Database from November 2012 to March 2015. Adult patients were included if they had a hospital encounter for PE (an International Classification of Diseases, Ninth Revision code = 415.1×) in the primary position, a claim for ≥1 diagnostic test for PE on day 0 to 2, and initiated rivaroxaban or parenteral anticoagulation/warfarin. Rivaroxaban users (allowing ≤2 days of prior parenteral therapy) were 1:1 propensity score matched to patients receiving parenterally bridged warfarin. Length of stay, total costs, and readmission for venous thromboembolism (VTE) or major bleeding during the same or subsequent 2 months following the index event were compared between cohorts. Analysis restricted to patients with low-risk PE was also performed.. Characteristics of the matched PE cohorts (n = 3466 per treatment) were well balanced. Rivaroxaban use was associated with a 1.36-day shorter LOS and $2304 reduction in total costs compared to parenterally bridged warfarin ( P < .001 for both). Rates of readmission for VTE were similar between cohorts (1.7% vs 1.6%; P = .64). No difference was observed between treatments for readmission for major bleeding (0.2% vs 0.2%; P > .99). In analyses restricted to low-risk patients (n = 1551 per treatment), rivaroxaban was associated with a 1.01-day and a $1855 reduction in LOS and costs, respectively ( P < .001 for both). Rates of readmission were again similar between treatments ( P > .56 for all).. Rivaroxaban significantly reduced hospital LOS and costs compared to parenterally bridged warfarin, without increasing the risk of readmission.

Topics: Adolescent; Adult; Aged; Costs and Cost Analysis; Female; Hemorrhage; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Warfarin; Young Adult

Venous aneurysms are a rare pathology that was first reported in the literature in 1968. Popliteal venous aneurysms (PVAs) are the most common lower limb venous aneurysm and have significant consequences including deep vein thrombosis, pulmonary embolus (PE), and death. A 52-year-old woman presented with chest pain and shortness of breath. A computed tomography (CT) angiography demonstrated bilateral pulmonary emboli, and she was commenced on rivaroxaban. History revealed no significant risk factors, and a thrombophilia screen was negative. However, an aneurysmal popliteal vein as seen on an ultrasound scan that was further clarified with CT venography. She underwent an uncomplicated open tangential resection and lateral venorrhaphy. The diagnosis of PVA is usually made incidentally during investigations for pulmonary embolism or chronic venous insufficiency. Surgery is indicated in all symptomatic patients with PE as anticoagulation alone is inadequate in these patients. Surgery is also recommended in patients with asymptomatic saccular aneurysms or large (>20 mm) fusiform aneurysms. The current mainstay of treatment for PVAs is open surgical management.

Topics: Aneurysm; Anticoagulants; Computed Tomography Angiography; Female; Humans; Middle Aged; Phlebography; Popliteal Vein; Pulmonary Embolism; Risk Factors; Rivaroxaban; Treatment Outcome; Vascular Surgical Procedures

We sought to compare length-of-stay (LOS), total hospital costs, and readmissions among pulmonary embolism (PE) patients treated with rivaroxaban versus parenterally bridged warfarin. We identified adult PE (primary diagnostic code = 415.1x) patients in the Premier Database (11/2012-9/2015), and included those with ≥1 PE diagnostic test on days 0-2. Rivaroxaban users (allowing ≤2 days of prior parenteral therapy) were 1:1 propensity score matched to patients parenterally bridged to warfarin. LOS, total costs, and readmission for venous thromboembolism (VTE) or major bleeding within the same or subsequent 2 months were compared between cohorts. Separate analyses were performed in low-risk PE patients. Rivaroxaban use was associated with a 1.4-day [95 % confidence interval (CI) -1.47 to -1.28] shorter LOS, and $2322 (95 % CI -$2499 to -$2146) reduction in costs compared to parenterally bridged warfarin (p < 0.001 for both). There was no difference in readmission for VTE (1.5 versus 1.7 %) or major bleeding (0.3 versus 0.2 %) between the rivaroxaban and parenterally bridged warfarin cohorts (p ≥ 0.27 for both). Results were similar in low-risk patients (0.2-1.0 day and $251-$1751 reductions in LOS and costs, respectively, p ≤ 0.01 for all). In patients with PE, rivaroxaban was associated with reduced LOS and costs, without increased risk of readmission versus parenterally bridged warfarin. Similar results were observed in low-risk PE patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Cost-Benefit Analysis; Female; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Multivariate Analysis; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Warfarin

Rivaroxaban has been shown to have similar efficacy but less major bleeding than warfarin in randomized trials of patients experiencing venous thromboembolism (VTE). This report sought to assess healthcare costs up to 12-months following an index VTE in patients prescribed either rivaroxaban or warfarin.. This study analyzed claims from the MarketScan Commercial Claims and Encounters Database from November 2011-July 2015. It selected adults newly-diagnosed with VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) if they had an outpatient prescription claim for rivaroxaban or warfarin within 7-days of the index event. Warfarin users were 2:1 propensity-score matched to rivaroxaban users and followed until the end of insurance coverage, end of data availability or 12-months of follow-up. Total per patient healthcare costs, including inpatient, outpatient, and overall pharmacy costs, were compared using a multivariable generalized linear model.. In total, 10,929 rivaroxaban patients were matched to 21,858 warfarin patients. Mean follow-up for rivaroxaban and warfarin patients was 317- and 321-days for those experiencing an index DVT, and 313- and 318-days for those with PE. Mean overall treatment costs per patient were lower for rivaroxaban vs warfarin users (-$1,116, p = .0016). This cost difference was driven by lower inpatient (-$622) and outpatient (-$1,156) treatment costs, and the higher pharmacy costs ($661) were, therefore, fully offset. Results were similar when analysis was restricted to DVT patients. No significant difference in total costs was observed in patients experiencing an index PE.. Claims databases are subject to inaccuracies and missing data. Prescription claims may not fully reflect actual medication utilization. Despite propensity-score matching and regression, residual confounding cannot be excluded.. Rivaroxaban was associated with significantly lower total per patient VTE treatment costs, despite higher pharmacy costs. These savings are the result of decreased inpatient and outpatient healthcare utilization costs associated with rivaroxaban.

Topics: Adult; Anticoagulants; Databases, Factual; Factor Xa Inhibitors; Female; Health Expenditures; Humans; Male; Middle Aged; Propensity Score; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Warfarin

The factor Xa inhibitors have been widely used for the treatment and prevention of venous thromboembolism (VTE). However, the efficacy of factor Xa inhibitors in Japanese patients with VTE has not been well examined. In this study, we investigated the effect of the sequential use of two factor Xa inhibitors in patients with acute VTE.. We conducted an observational study of 87 consecutive patients diagnosed with VTE. As an initial treatment, we administered subcutaneous fondaparinux to the patients for 7-10 days, and then switched to oral rivaroxaban. The symptoms and findings were assessed after the initial treatment and after using rivaroxaban for 7-14 days. We evaluated the deep vein thrombosis (DVT) in the legs using our own scoring system [quantitative ultrasound thrombosis (QUT) score].. Of the 87 patients, 33% had symptoms, half had pulmonary embolism (PE), and 95% had DVT of the legs. Out of the 87 patients, VTE worsened during the administration of fondaparinux in 4 patients. All of them had experienced malignancy, and died within 6 months. Of two patients developing bleeding, one patient required a transfusion. Eventually, this strategy was effective in 80 patients and had no change in one. The D-dimer level was significantly reduced by fondaparinux (17.8μg/ml±16.0μg/ml vs. 8.3μg/ml±7.2μg/ml, p<0.0001), followed by rivaroxaban (8.3μg/ml±7.2μg/ml vs. 5.5μg/ml±4.9μg/ml, p<0.0001). Similarly, the QUT score was improved by fondaparinux (4.7±2.6 vs. 2.5±2.5, p<0.0001), and further reduced by rivaroxaban (2.5±2.5 vs. 1.9±1.8, p<0.0001).. A treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute VTE in Japanese patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Unlike rivaroxaban, treatment of patients with pulmonary embolism (PE) with warfarin requires parenteral bridging and coagulation monitoring that may prolong length-of-stay (LOS) and increase hospital costs.. The aim of this study was to compare LOS, hospital costs and readmissions in PE patients managed through observation stays treated with rivaroxaban or parenterally bridged warfarin.. Premier Hospital claims data from November 2012 to March 2015 were used to identify patients with a primary diagnosis code for PE managed through an observation stay and with ≥1 claim for a PE-related diagnostic test on day 0-2. Rivaroxaban users, allowing ≤2 days of prior parenteral therapy, were 1:1 propensity-score matched to patients receiving parenterally bridged warfarin. LOS, the proportion of encounters lasting >2 midnights, total hospital costs of the index visit and risk of readmission for venous thromboembolism (VTE) or major bleeding during the same month or 2 months subsequent to the index event were compared between matched cohorts using multivariable regression.. A total of 312 rivaroxaban users were matched to 312 patients receiving parenterally bridged warfarin. Rivaroxaban was associated with an average of 0.27-day shorter LOS, a 52% decreased odds of an encounter lasting >2 midnights and a $403 mean reduction in costs vs parenterally bridged warfarin (P≤.002 for all). The readmission rate for VTE during the same or subsequent 2 months following the index PE was similar between cohorts (P=.75). No patient in either cohort was readmitted for major bleeding.. Rivaroxaban was associated with shortened LOS and lowered cost vs parenterally bridged warfarin in PE observation stay patients, without increases in the short-term rate of complications or readmission.

Topics: Administrative Claims, Healthcare; Adult; Aged; Anticoagulants; Female; Hemorrhage; Hospital Costs; Humans; Length of Stay; Male; Middle Aged; Observation; Patient Readmission; Propensity Score; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Warfarin

Since first used in 2009, non-vitamin K oral anticoagulants (NOAC) have gained world-wide acceptance. Two groups of NOAC are currently used: the direct thrombin antagonist dabigatran and three direct factor  Xa antagonists apixaban, edoxaban, and ricaroxaban. With their increasing use for prevention of thromboembolism, the probability increases that NOAC-pretreated patients are admitted to emergency departments or intensive care units.The clinical challenge in NOAC preanticoagulated patients is to adequately cope with the given anticoagulated status of such patients. Because of their short half-life, many patients will be adequately treated with a "wait and see" approach, and surgeries and interventions are postponed until anticoagulant activities have totally subsided. In the few cases where immediate action is mandated, based on appropriate risk assessments it can be decided either to take the increased hemorrhagic risk of early intervention or to transfuse factor concentrates like PPSB or FEIBA which can safely reverse the anticoagulant activities of the three factor Xa antagonists (and potentially also of dabigatran). Recently a humanized Fab antibody fragment for dabigatran, idarucizumab, has been introduced onto the market, that can immediately reverse the anticoagulant effects of dabigatran. For the reversal of dabigatran, idarucizumab is therefore the drug of choice.In addition, in some specific indications of emergency and intensive care medicine, the primary use of a NOAC can be considered advantageous. Such indications are early cardioversion in patients admitted for new episodes of atrial fibrillation and patients with acute pulmonary embolism. For the widespread use of low-molecular-weight heparins in such indications, however, the decision to use a NOAC for anticoagulant therapy is frequently postponed to the treatment phase when the stabilized patient is already treated on the general ward.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Dabigatran; Electric Countershock; Emergency Service, Hospital; Factor Xa Inhibitors; Hemorrhage; Humans; Intensive Care Units; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombin; Thromboembolism; Vitamin K

Topics: Aged; Depressive Disorder, Major; Electroconvulsive Therapy; Factor Xa Inhibitors; Female; Humans; Klebsiella Infections; Pulmonary Embolism; Rivaroxaban

Early reports suggested that the risk of gastrointestinal bleeding (GIB) was higher for patients on non-vitamin K antagonist oral anticoagulants (NOACs) than for those on warfarin. We compared the incidence of GIB in our patients on NOACs with those on warfarin.. We used our VA pharmacy database to identify patients taking NOACs (dabigatran, rivaroxaban, and apixaban) or warfarin between January 2011 and June 2015, and used the VistA system to identify those who were hospitalized for GIB. We included only patients with clinically significant GIB, defined as documented GI blood loss with a hemoglobin drop ≥2 g/dl, hemodynamic instability, and/or need for endoscopic evaluation, angiography, or surgery.. We identified 803 patients on NOACs and 6,263 on warfarin. One hundred and fifty-eight patients on warfarin had GIB (2.5%), compared with only five patients (0.6%) on NOACs (odds ratio=4.13; 95% confidence interval: 1.69-10.09). Blood transfusion for GIB was significantly more common in patients on warfarin than on NOACs (64.6% vs. 20%, P=0.04). Within 90 days of GIB hospitalization, 12 patients (7.6%) in the warfarin group died, whereas there were no deaths in the NOAC group.. In our patients, the incidence of GIB for those on warfarin was more than four times that for those on NOACs. Blood transfusions for GIB were more common in warfarin patients, and no NOAC patients died of GIB. In contrast to early reports, our findings suggest that the risk of GIB and subsequent complications is considerably lower for patients on NOACs than for patients on warfarin.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Transfusion; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemoglobins; Humans; Incidence; Male; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

Eighty year old male patient with heart failure preserved ejection fraction (EF),\ Obstructive sleep apnea, peripherovascular disease admitted with increasing\ shortness of breath and found with pulmonary emboli. Baseline 2D-echocardiogram\ performed demonstrated preserved ejection fraction and a right\ thrombus in transit. Anticoagulation with weight based-low molecular\ weight heparin was given for six days. Follow-up echo performed demonstrated\ complete dissolution of right heart thrombi. Since there was complete dissolution\ of thrombi seen on right atrium, anticoagulation with Rivaroxaban was given instead.

Topics: Acute Disease; Aged, 80 and over; Anticoagulants; Echocardiography; Follow-Up Studies; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Male; Pulmonary Embolism; Rivaroxaban; Thrombosis

Results of treatment of 71 patients, suffering an acute idiopathic deep veins thrombo'\ sis (DVT) of lower extremities,were analyzed. In 32 (45.1%) patients rivaroxaban was\ applied, in 39 (54.9%) — varfarin. The term of anticoagulant therapy was determined in\ accordance to the D—dimers level. Recurrence of the DVT, of massive hemorrhage or\ pulmonary thromboembolism in the follow—up groups were absent. In 29 (74.4%)\ patientsa constant dose of varfarin was lined up during minimal recommended period.\ For reduction of the DVT occurrence risk a rivaroxaban may serve as an alternative to\ varfarin.

Topics: Adult; Aged; Anticoagulants; Biomarkers; Drug Administration Schedule; Female; Femoral Vein; Fibrin Fibrinogen Degradation Products; Humans; Leg; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis; Warfarin

Topics: Adolescent; Adult; Factor Xa Inhibitors; Female; Humans; Menorrhagia; Middle Aged; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis; Young Adult

Non-steroidal anti-inflammatory drugs have been associated with an increased risk of venous thromboembolism. We report for the first time, the case of a patient who developed massive pulmonary embolism after a long period of treatment with high doses of ibuprofen. A 65-year-old woman was admitted with severe dyspnea while on treatment with high doses of ibuprofen for diffuse spine pain due to arthrosis. A spiral computed tomography showed a massive pulmonary embolism. No other explanation for the thromboembolic disorder was found. She was successfully treated with therapeutic doses of low-molecular-weight heparin followed by rivaroxaban. Ibuprofen was discontinued and replaced by tramadol. High-dose ibuprofen is likely to have accounted for the life-threatening thromboembolic disorder.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Humans; Ibuprofen; Long Term Adverse Effects; Osteoarthritis, Spine; Pulmonary Embolism; Rivaroxaban; Tomography, Spiral Computed; Treatment Outcome

Topics: Adult; Computed Tomography Angiography; Female; Heparin; Humans; Lower Extremity; Pain; Point-of-Care Systems; Pulmonary Embolism; Rivaroxaban; Saphenous Vein; Ultrasonography; United States; Venous Thrombosis

Novel (or non-vitamin K antagonist) oral anti-coagulants (NOACs) are antagonists of coagulation factors (F) Xa (rivaroxaban) or IIa (dabigatran), and their non-inferiority compared with vitamin K antagonists has been demonstrated in patients with non-valvular atrial fibrillation. However, it is still not fully understood if and how dabigatran and rivaroxaban impact platelet function. This observational study aimed to assess platelet function in patients receiving dabigatran or rivaroxaban.. This was a single centre, observational study quantifying platelet aggregation in 90 patients treated with NOACs by multiple electrode aggregometry. The thrombin receptor activating peptide (TRAP)-induced platelet aggregation was significantly higher in 35 patients receiving dabigatran (d) compared with control (c) patients (d 108±31 vs. c 85±30arbitrary units [AU]∗min, p<0.001). Patients receiving rivaroxaban (r) showed no differences compared with the control group (r 88±32 vs. c 85±30AU∗min, p=0.335). In intraindividual time courses of 16 patients, a significantly higher aggregation was found after the administration of dabigatran (before vs. after; 83±29 vs. 100±31AU∗min, p=0.009).. In this observational study, the TRAP-induced platelet aggregation was enhanced in cardiovascular patients receiving dabigatran. This might be explained by a change in the expression profile of thrombin receptors on the surface of platelets. Rivaroxaban had no influence on platelet aggregation.

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Blood Platelets; Dabigatran; Female; Humans; Male; Middle Aged; Platelet Aggregation; Pulmonary Embolism; Receptors, Thrombin; Rivaroxaban; Venous Thrombosis

Outpatient treatment of acute venous thromboembolism (VTE) requires the selection of patients with a low risk of bleeding during the first few weeks of anticoagulation. The accuracy of four systems, originally derived for predicting bleeding in VTE treated with vitamin K antagonists (VKAs), was assessed in VTE patients treated with rivaroxaban.. All patients treated with rivaroxaban in the multinational EINSTEIN deep vein thrombosis (DVT) and pulmonary embolism (PE) trials were included. Major bleeding was defined as ≥2 g/dL drop in hemoglobin or ≥2-unit blood transfusion, bleeding in critical area, or bleeding contributing to death. The authors examined the incidence of major bleeding in patients with low-risk assignment by the systems of Ruiz-Gimenez et al. (score = 0 to 1), Beyth et al. (score = 0), Kuijer et al. (score = 0), and Landefeld and Goldman. (score = 0). For clinical relevance, the definition of low risk for all scores except Kuijer includes all patients < 65 years with no prior bleeding history and no comorbid conditions (current cancer, renal insufficiency, diabetes mellitus, anemia, prior stroke, or myocardial infarction).. A total of 4,130 patients (1,731 with DVT only, 2,399 with PE with or without DVT) were treated with rivaroxaban for a mean (±SD) duration of 207.6 (±95.9) days. Major bleeding occurred in 1.0% (40 of 4,130; 95% confidence interval [CI] = 0.7% to 1.3%) overall. Rates of major bleeding for low-risk patients during the entire treatment period were similar: Ruiz-Gimenez et al., 12 of 2,622 (0.5%; 95% CI = 0.2% to 0.8%); Beyth et al., nine of 2,249 (0.4%; 95% CI = 0.2% to 0.8%); Kuijer et al., four of 1,186 (0.3%; 95% CI = 0.1% to 0.9%); and Landefeld and Goldman, 11 of 2,407 (0.5%; 95% CI = 0.2% to 0.8%). At 30 days, major bleed rates for low-risk patients were as follows: Ruiz-Gimenez et al., five of 2,622 (0.2%; 95% CI = 0.1% to 0.4%); Beyth et al., five of 2,249 (0.2%; 95% CI = 0.1% to 0.5%); Kuijer et al., three of 1,186 (0.3%; 95% CI = 0.1% to 0.7%); and Landefeld and Goldman, seven of 2,407 (0.3%; 95% CI = 0.1% to 0.6%). No low-risk patient had a fatal bleed.. Four scoring systems that use criteria obtained in routine clinical practice, derived to predict low bleeding risk with VKA treatment for VTE, identified patients with less than a 1% risk of major bleeding during full-course treatment with rivaroxaban.

Topics: Aged; Anticoagulants; Clinical Decision-Making; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Predictive Value of Tests; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data about rivaroxaban use in routine clinical practice are needed.. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007.. Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 [95% CI 0·54-1·54], p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 [95% CI 0·24-1·07], p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 [36·0%] of 2619 in the rivaroxaban group vs 805 [37·5%] of 2149 in the standard anticoagulation group).. In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings.. Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1 to 4 trials compared rivaroxaban 10 mg daily with commonly used doses of enoxaparin and demonstrated similar rates of VTE and bleeding.. To evaluate bleeding events between patients who received enoxaparin or rivaroxaban for prevention of venous thromboembolism (VTE) following total hip arthroplasty (THA) or total knee arthroplasty (TKA).. Retrospective cohort that compared patients undergoing THA and TKA who received enoxaparin (enoxaparin) with those who received rivaroxaban (rivaroxaban) and also with those who received enoxaparin in the RECORD 1 to 4 trials (enoxaparin RECORD). The primary outcome was any postoperative bleeding, defined as a composite of major and clinically relevant nonmajor bleeding based on the definitions in the RECORD 1 to 4 trials.. There was a lower rate of any postoperative bleeding (2.2% vs 6.8%, P = 0.004) in patients who received enoxaparin compared with rivaroxaban, and bleeding rates between the enoxaparin group and the enoxaparin RECORD groups were similar (2.2% vs 2.5%, P = 0.085). Major bleeding in the enoxaparin group (0.2%) was not significantly different from that in the rivaroxaban group (1.4%, P = 0.12) or the RECORD group (0.2%, P = 0.93). Clinically relevant nonmajor bleeding was also lower in the enoxaparin group compared with the rivaroxaban group (2.0% vs 5.5%, P = 0.012).. The use of enoxaparin for VTE prophylaxis following THA and TKA was associated with a lower rate of the primary outcome (any postoperative bleeding) compared with the use of rivaroxaban in a similar cohort of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Humans; Male; Middle Aged; Postoperative Hemorrhage; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Young Adult

Topics: Adult; Age Distribution; Aged; Anticoagulants; Bosentan; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Incidence; Latvia; Male; Middle Aged; Phenylpropionates; Prevalence; Pulmonary Embolism; Pyrazoles; Pyridazines; Pyridones; Registries; Rivaroxaban; Sex Distribution; Sildenafil Citrate; Sulfonamides; Vasodilator Agents; Warfarin; Young Adult

Imaging work-up of a 80-year-old woman with sudden onset of dyspnea during current rivaroxaban therapy: computer tomography angiography revealed fulminant bilateral pulmonary embolism. Furthermore, a serpentine-like huge mass in the right atrium was detected, highly suggestive of thrombus or a giant chiari network, respectively. This case highlights the importance of adequate dose regimen of factor Xa inhibitors, as well as the need of thorough differential diagnostic considerations of net like structures in the right atrium.

Topics: Aged, 80 and over; Atrial Fibrillation; Computed Tomography Angiography; Drug Dosage Calculations; Drug Substitution; Dyspnea; Factor Xa Inhibitors; Female; Heart Diseases; Heparin; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Treatment Outcome

To describe the clinical use of rivaroxaban in the treatment of 4 dogs with vascular thrombosis, 2 with pulmonary thromboembolism and 2 with systemic thrombosis.. This report describes the use of a direct factor Xa anticoagulant newly approved in human patients for the treatment or prevention of arterial or venous thrombosis. The use of this medication in a clinical setting for canine patients with thromboembolism has not been described before. Two patients were treated with rivaroxaban for pulmonary thromboembolism. Decreases in thrombus size were seen in both patients, but one patient suffered acute respiratory distress and was euthanized while the other continued to do well at the time of this writing. The other 2 patients were treated for systemic thrombosis. Decreases in thrombus size were also noted. One patient later suffered hematochezia of unknown cause, and the other continued to do well at the time of this writing.. This is the first published report of the use of a new oral direct factor Xa anticoagulant in dogs in a clinical setting for the treatment of both pulmonary and systemic thrombosis. In this case series, we share our limited experience in the use of this new medication, our strategy in determining appropriate dosages, and our monitoring protocol.

Topics: Animals; Dog Diseases; Dogs; Factor Xa Inhibitors; Female; Male; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

This study aimed to compare medication adherence and treatment persistence of patients on warfarin versus rivaroxaban in Singapore. A secondary objective was to identify significant covariates influencing adherence.. A retrospective cohort study was conducted where data from September 2009 to October 2014 was retrieved from the hospital electronic databases. Prescription records of rivaroxaban patients with 3 months or more of continuous prescription were extracted and compared against those of patients on warfarin. Primary outcome of adherence was determined based on the medication possession ratio (MPR), while treatment persistence was determined by outpatient clinic appointment gaps.. A total of 94 rivaroxaban and 137 warfarin users were analysed by complete case analysis. The MPR of warfarin patients was lower than rivaroxaban patients by 10% (95% CI, 6.4% to 13.6%; P <0.0001). Also, there were more warfarin patients who had gaps in treatment persistence compared to those prescribed rivaroxaban (8.0% vs 1.1%; P = 0.03). Significant factors affecting medication adherence were age and duration of anticoagulant use. For every 10-year increase in age, MPR increased by 1.7% (95% CI, 0.7% to 2.8%). Similarly, for every year increase in duration of use, MPR increased by 1.8% (95% CI, 0.6% to 3.0%). Race, gender, concomitant medication and type of residence were not found to be significant covariates in the multivariable analysis.. Patients on rivaroxaban are likely to be more adherent to their prescribed oral anticoagulant with increasing age and duration of treatment influencing adherence.

Topics: Adult; Age Factors; Anticoagulants; Databases, Factual; Factor Xa Inhibitors; Female; Humans; Male; Medication Adherence; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Singapore; Venous Thrombosis; Warfarin

Topics: Chemical and Drug Induced Liver Injury; Computed Tomography Angiography; Disease Management; Female; Humans; Middle Aged; Pulmonary Embolism; Rivaroxaban

We investigated three-month clinical outcomes in patients with venous thromboembolism (VTE) treated with rivaroxaban or conventional anticoagulation in routine clinical practice. Between November 2012 and February 2015, 2,062 consecutive patients with VTE from 11 acute care hospitals in Switzerland were enrolled in the SWIss Venous ThromboEmbolism Registry (SWIVTER). Overall, 417 (20 %) patients were treated with rivaroxaban. In comparison to 1,645 patients on conventional anticoagulation, patients on rivaroxaban were younger (56 ± 18 vs. 65 ± 17 years; p<0.001), less often had pulmonary embolism (38 % vs 66 %; p<0.001), hypertension (26 % vs 41 %; p<0.001), cancer (10 % vs 28 %; p<0.001), congestive heart failure (10 % vs 17 %; p=0.001), diabetes (8 % vs 15 %; p<0.001), chronic lung disease (7 % vs 13 %; p=0.001), renal insufficiency (7 % vs 13 %; p=0.001), recent surgery (7 % vs 14 %; p<0.001), and acute coronary syndrome (1 % vs 4 %; p=0.009). VTE reperfusion therapy was more frequently used (28 % vs 9 %; p<0.001) and indefinite-duration anticoagulation treatment less often planned (26 % vs 39 %; p<0.001), respectively. In the propensity score-adjusted population, the risk of recurrent VTE was similar in patients on rivaroxaban vs conventional anticoagulation (1.2 % vs 2.1 %, hazard ratio [HR] 0.55, 95 % confidence interval [CI] 0.18-1.65; p=0.29); the risk of major bleeding was also similar, respectively (0.5 % vs 0.5 %, HR 1.00, 95 %CI 0.14-7.07; p=1.00). Conventional anticoagulation is still frequently used for the treatment of VTE, particularly in the elderly and those with comorbidities. Early clinical outcomes were comparable between propensity score-adjusted patient populations on rivaroxaban and conventional anticoagulation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pulmonary Embolism; Registries; Retrospective Studies; Rivaroxaban; Switzerland; Thrombolytic Therapy; Treatment Outcome; Venous Thromboembolism

Thromboembolic disorders frequently require antithrombotic treatment during pregnancy and lactation. Vitamin K antagonists and heparins are the treatment options of choice in breastfeeding women. Factors including the route of administration, discomfort during treatment, and fetal and neonatal safety affect women's choices about anticoagulant therapy. Direct-acting oral anticoagulants (DOACs) have emerged as alternatives to these agents and may offer advantages compared with vitamin K antagonists. As breastfeeding women were excluded from clinical trials evaluating DOACs, no safety and efficacy data are available for these special patients and, crucially, estimates for infant exposure are lacking. Therefore, the manufacturer recommends against using DOACs during the lactation period. We present the case of a patient who stopped breastfeeding owing to a diagnosis of postpartum cardiomyopathy. Anticoagulation with enoxaparin that commenced after the diagnosis of postpartum pulmonary embolism was switched to rivaroxaban. At that time, breast milk samples were collected and rivaroxaban concentrations were determined by liquid chromatography tandem-mass spectrometry. Rivaroxaban appears in human breast milk in comparatively small amounts; its safety has not been determined.

Topics: Administration, Oral; Adult; Biological Availability; Breast Feeding; Chromatography; Computed Tomography Angiography; Drug Monitoring; Factor Xa Inhibitors; Female; Humans; Lung; Magnetic Resonance Imaging, Cine; Milk, Human; Pregnancy; Puerperal Disorders; Pulmonary Embolism; Rivaroxaban; Treatment Outcome

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Hospitalization; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes

Topics: Anticoagulants; Factor Xa Inhibitors; Hospitalization; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes

Compared with low-molecular-weight heparin (LMWH) and warfarin, the oral anticoagulant rivaroxaban has advantages, such as simplified care, that may lead to less health care resource utilization.. A retrospective, matched-cohort analysis was conducted using claims dated between January 2011 and December 2013 from the Truven Health Analytics MarketScan databases. Adult patients who had a primary diagnosis of deep vein thrombosis (DVT) during an outpatient or emergency room (ER) visit after November 2, 2012, and who were treated with rivaroxaban or LMWH/warfarin on the same day, were identified. Patients were observed over 1, 2, 3, and 4 weeks after the DVT diagnosis. The mean numbers of hospitalizations for all causes and for venous thromboembolism (VTE) (which included those for DVT or pulmonary embolism), as well as other health care resource utilization (ER, outpatient, and other visits), and the associated health care costs and pharmacy costs, were evaluated and compared between cohorts using the Lin method.. All of the 512 rivaroxaban-treated patients were well matched with the LMWH/warfarin-treated patients. The mean numbers of all-cause hospitalizations were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (0.012 vs 0.032; P = 0.044) and 2 weeks (0.022 vs 0.048; P = 0.040). The corresponding mean numbers of VTE-related hospitalizations were significantly lower with rivaroxaban over 1 week (0.008 vs 0.028; P = 0.020), 2 weeks (0.016 vs 0.042; P = 0.020), and 4 weeks (0.034 vs 0.068; P = 0.036). The mean numbers of all-cause and VTE-related outpatient visits were also significantly lower in rivaroxaban users compared with those in LMWH/warfarin users over 1, 2, 3, and 4 weeks (all, P < 0.001). In terms of all-cause and VTE-related ER and other visits, no statistically significant differences were found between cohorts over the first 4 weeks. The associated mean all-cause total health care costs were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (US $2332 vs $3428; P < 0.001) and 2 weeks ($3108 vs $4524; P < 0.001); moreover, significantly lower mean costs related to all-cause hospitalizations (weeks 1 and 2) and pharmacy (weeks 1-4) were observed in patients treated with rivaroxaban, while no differences were found in costs related to ER visits (weeks 1-4), outpatient visits (weeks 1-4), or other visits (with the exception of week 1).. Patients with DVT treated with rivaroxaban after an outpatient/ER visit had significantly lower mean numbers of hospitalizations and outpatient visits, as well as lower mean total, hospitalization, and pharmacy costs during the first 2 weeks of treatment compared with those in matched LMWH/warfarin users.

Topics: Adult; Aged; Anticoagulants; Databases, Factual; Female; Health Care Costs; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Outpatients; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Aged; Aged, 80 and over; Angiography; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Inpatients; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Tomography, X-Ray Computed; Treatment Outcome

To compare hospital length of stay (LOS) and hospital treatment costs in low-risk patients with pulmonary embolism (PE) anticoagulated with rivaroxaban or heparin bridging to warfarin therapy.. Retrospective review of electronic health records and hospital billing records.. Large, teaching hospital in the northeastern United States.. One hundred ninety adults with objectively confirmed acute PE presenting to the emergency department between November 1, 2012, and May, 12, 2015, who were classified as low risk of early mortality and received anticoagulation with either rivaroxaban or heparin (i.e., unfractionated heparin or low-molecular-weight heparin) bridging to warfarin therapy were included in the analysis. Patients were identified as low risk by at least one of the following prediction rules: simplified Pulmonary Embolism Severity Index (sPESI; 115 patients), Hestia criteria (87 patients), or In-hospital Mortality for Pulmonary Embolism using Claims Data (IMPACT; 108 patients); these were not mutually exclusive, as patients could be classified as low risk by more than one risk stratification tool.. We divided low-risk patients identified by each prediction rule into two cohorts: those receiving rivaroxaban (allowing ≤ 2 days of prior heparin use) or heparin bridging to warfarin therapy. The primary end points for this study were LOS (number of days from the patient's arrival at our institution until discharge) and total hospital treatment costs (our institution's actual costs to provide treatment) for the index PE hospital encounter. Using multivariable generalized linear model regression (gamma-distributed error and log-link), we estimated differences in LOS and hospital costs (in 2015 U.S. dollars) between the two cohorts after covariate adjustment. Rivaroxaban was associated with significantly shorter adjusted LOS (range -2.1 to -4.3 days) and significantly lower index hospital costs (range -$3835 to -$7094) versus heparin bridging to warfarin, regardless of the prediction rule used to identify low-risk patients.. Among low-risk PE patients identified by using sPESI, Hestia or IMPACT, rivaroxaban was associated with significantly shorter LOS and lower hospital treatment costs versus heparin bridging to warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Health Care Costs; Heparin; Heparin, Low-Molecular-Weight; Hospital Mortality; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Warfarin

Using real-world data, this study compares inpatient length of stay (LOS) and costs for patients with a primary diagnosis of pulmonary embolism (PE) initiating treatment with oral anticoagulation with rivaroxaban versus warfarin.. Hospitalizations from MarketScan's Hospital Drug Database were selected from November 1, 2012, through December 31, 2013, for adults with a primary diagnosis of PE initiating treatment with rivaroxaban or warfarin. Warfarin patients were matched 1:1 to rivaroxaban patients using exact and propensity score matching. Hospital LOS, treatment patterns, and hospitalization costs were evaluated.. Matched cohorts included 751 rivaroxaban-treated patients and 751 warfarin-treated patients. Adjusted mean LOS was 3.77 days for rivaroxaban patients (95% CI, 3.66-3.87 days) and 5.48 days for warfarin patients (95% CI, 5.33-5.63 days; P < .001). Mean (SD) LOS was shorter for patients taking rivaroxaban whether admission was for provoked PE (rivaroxaban: 5.2 [5.1] days; warfarin: 7.0 [6.5] days; P < .001) or unprovoked PE (rivaroxaban: 3.4 [2.3] days; warfarin: 5.1 [2.7] days; P < .001). Mean (SD) days from first dose to discharge were 2.5 (1.7) (rivaroxaban) and 4.0 (2.9) (warfarin) when initiated with parenteral anticoagulants (P < .001) and 2.7 (1.7) (rivaroxaban) and 4.0 (2.2) (warfarin) without parenteral anticoagulants (P < .001). The rivaroxaban cohort incurred significantly lower unadjusted mean (SD) hospitalization costs (rivaroxaban: $8473 [$9105]; warfarin: $10,291 [$9185]; P < .001), confirmed by covariate adjustment with generalized linear modeling estimating predicted mean hospitalization costs of $8266 for rivaroxaban patients (95% CI, $7851-$8681) and $10,511 for warfarin patients (95% CI, $10,031-$10,992; P < .001).. patients with PE treated with rivaroxaban incurred significantly lower hospitalization costs by $2245 per admission compared with patients treated with warfarin, which was attributable to cost offsets from 1.71 fewer days of stay in the hospital.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hospital Costs; Hospitalization; Humans; Inpatients; Length of Stay; Male; Middle Aged; Propensity Score; Pulmonary Embolism; Rivaroxaban; Warfarin; Young Adult

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, results in a substantial healthcare system burden. This retrospective observational study compared hospital length of stay (LOS) and hospitalization costs for patients with venous thromboembolism treated with rivaroxaban versus those treated with warfarin.. Hospitalizations for adult patients with a primary diagnosis of deep vein thrombosis or pulmonary embolism who were initiated on rivaroxaban or warfarin were selected from MarketScan's Hospital Drug Database between November 1, 2012, and December 31, 2013. Patients treated with warfarin were matched 1:1 to patients treated with rivaroxaban using exact and propensity score matching. Hospital LOS, time from first dose to discharge, and hospitalization costs were reported descriptively and with generalized linear models (GLMs). The final study cohorts each included 1223 patients (751 with pulmonary embolism and 472 with deep vein thrombosis). Cohorts were well matched for demographic and clinical characteristics. Mean (±SD) LOS was 3.7±3.1 days for patients taking rivaroxaban and 5.2±3.7 days for patients taking warfarin, confirmed by GLM-adjusted results (rivaroxaban 3.7 days, warfarin 5.3 days, P<0.001). Patients with provoked venous thromboembolism admissions showed longer LOSs (rivaroxaban 5.1±4.5 days, warfarin 6.5±5.6 days, P<0.001) than those with unprovoked venous thromboembolism (rivaroxaban 3.3±2.4 days, warfarin 4.8±2.8 days, P<0.001). Days from first dose to discharge were 2.4±1.7 for patients treated with rivaroxaban and 3.9±3.7 for patients treated with warfarin when initiated with parenteral anticoagulants (P<0.001), and 2.7±1.7 and 3.7±2.1, respectively, when initiated without parenteral anticoagulants (P<0.001). Patients initiated on rivaroxaban incurred significantly lower mean total hospitalization costs ($8688±$9927 versus $9823±$9319, P=0.004), confirmed by modeling (rivaroxaban $8387 [95% confidence interval, $8035-$8739]; warfarin $10 275 [95% confidence interval, $9842-$10 708]).. Rivaroxaban was associated with significantly shorter hospital LOS and lower hospitalization costs compared with warfarin.

Topics: Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Female; Hospital Costs; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; United States; Venous Thrombosis; Warfarin; Young Adult

Topics: Aged, 80 and over; Anticoagulants; Chest Pain; Endoscopy, Gastrointestinal; Esophagitis; Female; Humans; Pulmonary Embolism; Rivaroxaban; Tomography, X-Ray Computed; Treatment Outcome; Vomiting

Right atrial thrombus in the setting of a large pulmonary embolus is rare and is associated with serious adverse events. This case report presents the role played by EKOS EkoSonic ultrasound system in successfully treating right atrial thrombus and massive pulmonary embolism.. A 69-year-old female presented with a massive pulmonary embolus and a large mobile right atrial thrombus. She was treated with catheter-directed lysis using the EKOS EkoSonic ultrasound system and tissue plasminogen activator, with complete resolution of her right atrial thrombus and a marked improvement in her pulmonary embolus and hemodynamics.. This case report provides a new and an effective option to treat right atrial thrombus associated with a large pulmonary embolus leading to a good outcome.

Topics: Aged; Cardiac Catheterization; Combined Modality Therapy; Female; Heart Atria; Heparin; Humans; Mechanical Thrombolysis; Pulmonary Embolism; Recombinant Proteins; Rivaroxaban; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; Ultrasonic Therapy; Ultrasonography, Interventional

Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB.. We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death.. We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006-0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18-28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861-6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216-1.89, P=0.40).. Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Topics: Aged; Aged, 80 and over; Anticoagulants; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Enoxaparin; Female; Gastrointestinal Hemorrhage; Heparin; Humans; Ischemic Attack, Transient; Longitudinal Studies; Male; Middle Aged; Morpholines; Patient Readmission; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Venous Thrombosis; Warfarin; Withholding Treatment

Venous thromboembolism (VTE) impacts ∼900,000 individuals annually in the US, causing up to 100,000 deaths. Patients experiencing VTE have heightened risk of recurrence. Initial parenteral anti-coagulation is standard therapy for acute VTE followed by ≥3 months of warfarin, which introduces the risk of major bleeding. Balancing increased risks of bleeding and recurrent VTE remains challenging. Recent clinical trials suggest that rivaroxaban, an oral direct inhibitor of factor Xa, provides an effective, safe, simplified approach to treatment. This study considers the economic implications of these data.. This study modeled inpatient, acute, and 1-year VTE costs for a hypothetical commercial plan with 1 million members. At baseline, all VTE patients receive standard therapy. Alternatively, 25% are instead treated with rivaroxaban. Model inputs are trial- and literature-based.. Standard therapy for VTE consumes 9474 inpatient days ($31.6 million). Added to that is treatment for 74 recurrences ($1.4 million); major and non-major bleed events ($1 million); and direct costs of anti-coagulation ($5.3 million). Alternatively, a 25% shift to oral anti-coagulation with rivaroxaban reduces inpatient days (by 5%); associated acute-care costs (by 2%); recurrences and costs (by 6%). Four major bleeding events are prevented, at the cost of one additional non-major bleeding event, which, taken together, reduce net utilization by 9%. Direct costs of anti-coagulation increase by 5%.. The reduction in inpatient utilization, recurrences, and major bleeding resulting from a 25% shift from standard therapy to rivaroxaban following acute VTE would conserve ∼$860,475 for every 1 million commercial health plan enrollees.

Topics: Anticoagulants; Computer Simulation; Cost-Benefit Analysis; Drug Therapy, Combination; Enoxaparin; Hemorrhage; Hospitalization; Humans; Models, Econometric; Pulmonary Embolism; Recurrence; Rivaroxaban; United States; Venous Thromboembolism; Vitamin K

Medical costs that may be avoided when any of the four new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF) were estimated and compared. Additionally, the overall differences in medical costs were estimated for NVAF and venous thromboembolism (VTE) patient populations combined.. Medical cost differences associated with NOAC use vs warfarin or placebo among NVAF and VTE patients were estimated based on clinical event rates obtained from the published trial data. The clinical event rates were calculated as the percentage of patients with each of the clinical events during the trial periods. Univariate and multivariate sensitivity analyses were conducted for the medical-cost differences determined for NVAF patients. A hypothetical health plan population of 1 million members was used to estimate and compare the combined medical-cost differences of the NVAF and VTE populations and were projected in the years 2015-2018.. In a year, the medical-cost differences associated with NOAC use instead of warfarin were estimated at -$204, -$140, -$495, and -$340 per patient for dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, among the hypothetical population, the medical-cost differences were -$3.7, -$4.2, -$11.5, and -$6.6 million for NVAF and acute VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, for the combined NVAF, acute VTE, and extended VTE patient populations, medical-cost differences were -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban, respectively. Medical-cost differences associated with use of NOACs were projected to steadily increase from 2014 to 2018.. Medical costs are reduced when NOACs are used instead of warfarin/placebo for the treatment of NVAF or VTE, with apixaban being associated with the greatest reduction in medical costs.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Costs and Cost Analysis; Dabigatran; Health Expenditures; Hemorrhage; Humans; Models, Econometric; Myocardial Infarction; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; United States; Venous Thromboembolism; Warfarin

Rivaroxaban is increasingly used to treat patients with acute venous thromboembolism (VTE), a potentially life-threatening condition. Because absorption of rivaroxaban decreases from nearly 100% to 66% under fasting conditions, it is recommended that VTE patients take rivaroxaban with a meal. However, this recommendation is based on preclinical pharmacokinetic (PK) studies in healthy volunteers. So far, no clinical evidence is available to support this recommendation. We describe a case of a compliant young patient who developed recurrent pulmonary embolism during rivaroxaban treatment. PK studies provided evidence that malabsorption of rivaroxaban 20 mg due to irregular intake of meals during shift work was the leading cause of recurrent pulmonary embolism. When the patient was instructed to take rivaroxaban with a regular meal, peak plasma concentrations increased from 115 to 318 ng mL(-1) (+ 176%). Consequently, the importance of taking rivaroxaban with food may have a greater clinical relevance than data from preclinical PK studies suggest.

Topics: Adult; Blood Coagulation Tests; Drug Monitoring; Factor Xa Inhibitors; Food-Drug Interactions; Humans; Job Description; Male; Meals; Medication Adherence; Personnel Staffing and Scheduling; Predictive Value of Tests; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Acute Disease; Anticoagulants; Guideline Adherence; Heparin; Humans; Morpholines; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Thiophenes; Vitamin K

Target-specific anticoagulants such as rivaroxaban facilitate immediate discharge of low-risk venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) allowing treatment at home instead of hospitalization.. The objective was to compare costs accrued over 6 months by patients diagnosed with low-risk VTE and treated at home with rivaroxaban versus usual care with heparin-warfarin.. This case-control study calculated costs using the established charge-to-cost ratio from UB-04 billing claims of patients diagnosed at two metropolitan hospitals. Patients were defined as low risk by the Hestia criteria. All patients were anticoagulated for 6 months. Control patients were treated with usual care using low-molecular-weight heparin (LMWH) and then warfarin. Case patients were treated with an initial dose of rivaroxaban in the ED followed by same-day discharge home with rivaroxaban. Medians were compared by Mann-Whitney U-test.. Fifty cases and 47 controls were identified. Groups were well matched according to mean age, Charlson comorbidity score, and proportions by sex and location of thrombus. For all VTEs, median hospital charges for 6 months after diagnosis were $11,128 (interquartile range [IQR] = $8,110 to $23,390) for controls, compared with $4,787 (IQR = $3,042 to $7,596) for cases (Mann-Whitney U-test p < 0.001). Subgroup analyses of the first week of therapy, PE, DVT, and inpatient pharmacy costs retained significance, with costs for rivaroxaban-treated PE patients 57% lower than control PE patients (p < 0.001) and 56% lower for DVT patients (p = 0.003).. Cost of medical care was lower for low-risk VTE patients discharged immediately from the ED with rivaroxaban therapy compared with patients treated with LMWH-warfarin.

Topics: Adult; Aged; Anticoagulants; Case-Control Studies; Emergency Service, Hospital; Female; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Statistics, Nonparametric; Venous Thrombosis; Warfarin

The study hypothesis was that a target-specific anticoagulant would allow successful home treatment of selected patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) diagnosed in two urban emergency departments (EDs).. A protocol was established for treating low-risk DVT or PE patients with rivaroxaban and clinic, follow-up at both 2 to 5 weeks, and 3 to 6 months. Patients were determined to be low-risk by using a modified version of the Hestia criteria, supplemented by additional criteria for patients with active cancer. Acceptable outcome rates were defined as venous thromboembolism (VTE) recurrence ≤ 2.1% or bleeding ≤ 9.4% during treatment. VTE recurrence required positive imaging of any VTE. The International Society of Thrombosis and Hemostasis definition of major or clinically relevant nonmajor bleeding was used.. From March 2013 through April 2014, a total of 106 patients were treated. Seventy-one (68%) had DVT, 30 (28%) had PE, and five (3%) had both, representing 51% of all DVTs and 27% of all PEs diagnosed in both EDs during the period of study. The 106 patients have been followed for a mean (±SD) of 389 (±111) days (range = 213 to 594 days). No patient had VTE recurrence, and no patient had a major or clinically relevant bleeding event while on therapy (none of the 106, 0%, 95% confidence interval [CI] = 0% to 3.4%). However, three patients 2.8% (95% CI = 1% to 8%) had recurrent DVT after cessation of therapy.. Patients diagnosed with VTE and immediately discharged from the ED while treated with rivaroxaban had a low rate of VTE recurrence and bleeding.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Emergency Service, Hospital; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Discharge; Patient Selection; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; United States; Venous Thrombosis; Young Adult

To establish the rat model of acute pulmonary embolism, and study the changes of vascular active substances in pulmonary embolism rats, and investigate the interventive effect of anticoagulant drugs on vascular active substances.. One hundred and twenty-eight rats were randomly divided into four groups: control group, model group, low-molecular-weight heparin and warfarin treated group and rivaroxaban-treated group (n = 32 in each group). The method of autologous thrombosis was used to establish the animal model of acute pulmonary embolism. The animals were treated with saline or different anticoagulant drugs. The physiological and biochemical parameters were detected at different time points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d or 1 week respectively and the pathologic samples of lung tissues were collected to analyze the pulmonary pathological changes in different groups.. Rats in embolization group after blood clots injection showed shortness of breath, oral cyanosis; quicken heart rates and other symptoms. All embolization groups had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended to the normal levels in the control group. The pulmonary hypertensions were gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the same as that of the low molecular weight heparin or warfarin.. Anticoagulation therapy can effectively improve endothelial function after pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP levels to normal levels. The efficacy of rivaroxaban is not inferior to that of low molecular weight heparin and warfarin.

Topics: Animals; Anticoagulants; Disease Models, Animal; Endothelin-1; Heparin, Low-Molecular-Weight; Hypertension, Pulmonary; Lung; Morpholines; Pulmonary Embolism; Rats; Rivaroxaban; Thiophenes; Warfarin

Topics: Acute Kidney Injury; Aged; Anticoagulants; Echocardiography; Embolectomy; Factor Xa Inhibitors; Heparin; Humans; Hypertrophy, Right Ventricular; Male; Pulmonary Embolism; Recurrence; Rivaroxaban; Tachycardia, Sinus; Tomography, X-Ray Computed; Treatment Outcome

Topics: Acute Disease; Age Factors; Ambulatory Care; Anticoagulants; Antithrombins; Comorbidity; Dabigatran; Disease Management; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Neoplasms; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Thrombolytic Therapy; Tissue Plasminogen Activator; Vena Cava Filters; Warfarin

Topics: Anticoagulants; Emergency Service, Hospital; Female; Humans; Male; Pulmonary Embolism; Rivaroxaban; Venous Thrombosis

Rivaroxaban, a factor Xa inhibitor, is a direct-acting oral anticoagulant (DOAC) indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for reducing the risk of DVT and PE recurrence. To our knowledge, no data are presently available to guide DOAC dosing in the postpartum period when pharmacokinetic and pharmacodynamic changes induced by pregnancy have an impact on drug clearance and increase hypercoagulability for a period of 6-8 weeks after delivery. We describe the case of a 35-year-old postpartum woman who presented to the emergency department with a diagnosis of a new multiple segmental PE 5 days after starting rivaroxaban therapy for a diagnosis of DVT. No precipitating cause, including noncompliance, was identified as a source of thrombosis embolization or extension. The patient was admitted, a heparin infusion was started for the management of PE, and rivaroxaban was discontinued. She was transitioned to enoxaparin 1 mg/kg (90 mg) subcutaneously every 12 hours the next day, bridged to warfarin, and discharged home on the overlapping regimen with close follow-up by the pharmacist-managed outpatient Anticoagulation Management Service. To our knowledge, this is the first case report of potential failure associated with rivaroxaban therapy in the postpartum period, possibly due to pharmacokinetic alterations seen in the postpartum period contributing to decreased drug exposure, yielding reduced anticoagulant efficacy. Clinicians should carefully weigh the risks and benefits of DOAC therapy in postpartum patients or other special populations requiring anticoagulation therapy. This report also highlights the need for further research identifying the impact of pharmacokinetic changes induced by special populations and the need to develop monitoring assays for such clinical situations.

Topics: Administration, Oral; Adult; Factor Xa Inhibitors; Female; Humans; Postpartum Period; Pulmonary Embolism; Recurrence; Rivaroxaban; Treatment Failure

Pulmonary embolism remains one of the leading causes of cardiovascular mortality. The standard treatment for pulmonary embolism is anticoagulant therapy using low molecular weight heparin, fondaparinux and a vitamin K antagonist, but a recent clinical trial showed that rivaroxaban, an oral factor Xa inhibitor, was as effective as standard therapy for the initial and long-term treatment of pulmonary embolism and had less bleeding complications.. The present report describes the case of an 80-year-old white man with an intermediate to low early mortality risk of pulmonary embolism. He was successfully treated with rivaroxaban (administered orally as monotherapy), demonstrating rapid benefit without any adverse events.. Rivaroxaban, particularly in the acute phase of pulmonary embolism, may be considered an effective and safe therapeutic choice even in elderly patients, a population less represented in clinical trials.

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Dyspnea; Humans; Male; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Treatment Outcome

Topics: Administration, Oral; Dabigatran; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Substitution; Fibrinolytic Agents; General Practice; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thrombosis

Thrombolysis, though very effective, has not been embraced as routine therapy for symptomatic pulmonary embolism (PE) except in very severe cases. Rivaroxaban recently has been approved for the treatment of venous thromboembolism (VTE). There are no data on the combined use of thrombolysis and rivaroxaban in PE.. "Safe dose" thrombolysis (SDT) plus new oral anticoagulants are expected to become an appealing, safe and effective approach in the treatment of moderate and severe PE in the near future, thereby drastically reducing hospitalization time.. Over a 12-month period, 98 consecutive patients with symptomatic PE were treated by a combination of SDT and rivaroxaban. The SDT was started in parallel with unfractionated heparin and given in 2 hours. Heparin was given for a total of 24 hours and rivaroxaban started at 15 or 20 mg daily 2 hours after termination of heparin infusion.. There was no bleeding due to SDT. Recurrent VTE occurred in 3 patients who had been switched to warfarin. No patient on rivaroxaban developed VTE. Two patients died of cancer at a mean follow-up of 12 ± 2 months. The pulmonary artery systolic pressure dropped from 52.8 ± 3.9 mm Hg before to 32 ± 4.4 mm Hg within 36 hours of SDT (P < 0.001). The duration of hospitalization for patients presenting primarily for PE was 1.9 ± 0.2 days.. "Safe dose" thrombolysis plus rivaroxaban is highly safe and effective in the treatment of moderate and severe PE, leading to favorable early and intermediate-term outcomes and early discharge.

Topics: Administration, Oral; Aged; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Morpholines; Patient Discharge; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Severity of Illness Index; Thiophenes; Thrombolytic Therapy; Time Factors; Treatment Outcome

The prevalence of venous thromboembolism (VTE) has been increasing in China. However, the treatment pattern and economic burden of these patients have not been well-understood.. The objective of this study was to examine the patient characteristics, treatment pattern, anticoagulant monitoring, and economic burden of VTE among hospitalized patients in China.. Hospitalizations with a diagnosis of VTE [including deep vein thrombosis (DVT) or pulmonary embolism (PE)] between 1 January 2010 and 30 June 2013 were included. Descriptive analysis was conducted for patients' characteristics, anticoagulant treatment, international normalized ratio (INR) monitoring, and hospitalization cost [in 2013 Chinese yuan (Y) and US dollars (US$)]. Multivariate regressions were performed to assess factors associated with oral anticoagulant use and total costs of inpatient care.. A total of 1,047 VTE-related hospitalizations were selected. The sample had a mean age of 62.4 years, with 45.9 % female. About 46.3 % of hospitalizations used heparin only, 35.0 % used warfarin, 0.8 % used rivaroxaban, and 18.0 % did not use anticoagulants. Among hospitalizations where warfarin was used, 90.8 % received at least one INR test and only 30 % had the last INR within the target therapeutic range (2-3) before discharge. The mean (standard deviation) total cost per hospitalization was Y29,114 (43,772) [US$4,757 (7,152)]. PE, VTE as primary diagnosis, female, insurance coverage, anticoagulant treatment, co-morbidities, admission condition, and surgical procedure were significantly associated with inpatient costs.. Conventional anticoagulants were most commonly used in the study sample. Under-monitoring and suboptimal care may be an issue for patients treated with warfarin. The average total inpatient cost of VTE-related hospitalizations is high.

Topics: Anticoagulants; China; Female; Health Care Costs; Heparin, Low-Molecular-Weight; Hospitalization; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Morpholines; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

Rivaroxaban is the first oral factor Xa inhibitor approved in the US to reduce the risk of stroke and blood clots among people with non-valvular atrial fibrillation, treat deep vein thrombosis (DVT), treat pulmonary embolism (PE), reduce the risk of recurrence of DVT and PE, and prevent DVT and PE after knee or hip replacement surgery. The objective of this study was to evaluate the costs from a hospital perspective of treating patients with rivaroxaban vs other anticoagulant agents across these five populations.. An economic model was developed using treatment regimens from the ROCKET-AF, EINSTEIN-DVT and PE, and RECORD1-3 randomized clinical trials. The distribution of hospital admissions used in the model across the different populations was derived from the 2010 Healthcare Cost and Utilization Project database. The model compared total costs of anticoagulant treatment, monitoring, inpatient stay, and administration for patients receiving rivaroxaban vs other anticoagulant agents. The length of inpatient stay (LOS) was determined from the literature.. Across all populations, rivaroxaban was associated with an overall mean cost savings of $1520 per patient. The largest cost savings associated with rivaroxaban was observed in patients with DVT or PE ($6205 and $2742 per patient, respectively). The main driver of the cost savings resulted from the reduction in LOS associated with rivaroxaban, contributing to ∼90% of the total savings. Furthermore, the overall mean anticoagulant treatment cost was lower for rivaroxaban vs the reference groups.. The distribution of patients across indications used in the model may not be generalizable to all hospitals, where practice patterns may vary, and average LOS cost may not reflect the actual reimbursements that hospitals received.. From a hospital perspective, the use of rivaroxaban may be associated with cost savings when compared to other anticoagulant treatments due to lower drug cost and shorter LOS associated with rivaroxaban.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Computer Simulation; Cost Savings; Cost-Benefit Analysis; Factor Xa Inhibitors; Humans; Inpatients; Length of Stay; Models, Economic; Morpholines; Pulmonary Embolism; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Thiophenes; United States; Venous Thrombosis; Warfarin

Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute symptomatic VTE.. Open follow-up study of a cohort of patients aged 18 and over diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) treated with rivaroxaban from December 2011 to January 2014.. The total number of patients treated with rivaroxaban was 103. The mean age was 58+/-17 years. The most frequent co-morbidities were: hypertension (30.0%), dyslipidemia (23.3%) and respiratory disease (25.2%). The type of thromboembolic event treated was: DVT (64.1%), PE (18.4%), DVT+PE (17.5%). Of the rivaroxaban-treated patients, 30% did so from the initial anticoagulant therapy and the other 70% in long-term or extended anticoagulant therapy. The median time of treatment with rivaroxaban was 6 months [corrected]. There was one recurrence and no deaths occurred. Six patients had bleeding, one of which was severe.. Rivaroxaban provides a therapeutic alternative in a group of patients with VTE with advantages over VKAs, because of the convenience in dosing, lack of requirements for periodic monitoring and limited interaction with other drugs.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Selection; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Spain; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE.. A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily; n = 405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended 'bridging' therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio = 2.0-3.0; n = 401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset.. Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median = 1 day) compared with enoxaparin/VKA (mean = 4.5 vs 6.1; median = 3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients.. In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.

Topics: Adolescent; Adult; Aged; Anticoagulants; Enoxaparin; Female; Humans; Length of Stay; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; United States; Venous Thrombosis; Vitamin K; Young Adult

Hypercoagulability, resulting in thromboembolic events, can be a life-threatening complication of nephrotic syndrome (NS). Conventional anticoagulants, such as warfarin, have been the standard of care for more than 50 years; however, the availability of target-specific oral anticoagulants (TSOACs) have provided additional options for the treatment and prevention of thromboembolic events. Documented use of the TSOACs in patients with NS and hypercoagulability is currently limited.. We present the case of an 18-year-old young woman with NS and renal vein thrombosis who was readmitted with bilateral pulmonary emboli on therapeutic doses of warfarin, with a goal international normalized ratio of 2.0 to 3.0. The decision was made to transition the patient from warfarin to rivaroxaban, an oral factor Xa inhibitor.. Rivaroxaban was the first of the emerging TSOACs to be FDA approved for both prevention and treatment of venous thromboembolism. With favorable safety and efficacy data compared with warfarin in addition to a predictable pharmacokinetic profile and the lack of requirement of routine monitoring, rivaroxaban provides a useful alternative in this patient population.. While on therapeutic anticoagulation, a patient previously diagnosed with NS and renal vein thrombosis experienced pulmonary emboli on a conventional anticoagulant and was switched to a target-specific oral anticoagulant with documented completion of 6 months of therapy without recurrent thromboembolism.

Topics: Administration, Oral; Adolescent; Anticoagulants; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Morpholines; Nephrotic Syndrome; Pulmonary Embolism; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism; Warfarin

Topics: Dose-Response Relationship, Drug; Factor Xa Inhibitors; Humans; Morpholines; Practice Guidelines as Topic; Pulmonary Embolism; Rivaroxaban; Thiophenes

Nephrotic syndrom is an association of proteinuria>3g/d or 50mg/kg/d, an hypoalbuminemia<30g/L and a hypoproteinemia<60g/L. Primary etiologies are minimal glomerular injury, focal segmental glomerulosclerosis and non membranous glomerulonephritis. Secondary etiologies are diabetes, high blood pressure and amyloidosis. We present four cases about nephrotic syndrome after thromboembolic disease. In every case, patients show a pulmonary embolism symptomatic of a nephrotic syndrom, whose diagnostic could be delayed up to six months after first pulmonary symptoms. This raised the problem of renal biopsy in these patients who need anticoagulation. In minimal change nephrosis, without hematuria, high blood pressure or renal dysfonction, a corticosteroid therapy test could be done assuming that is corticosensitive minimal glomerular injury. In every case, anticoagulation course must be completed and maintained in case of patent nephrotic syndrom with an albuminemia under 20g/L. In case of pulmonary embolism or deep vein thrombosis, idiopathic-looking, a nephrotic syndrome must be sought-after. The two diagnosis ways are the proteinuria on the urine dipstick and the hypoproteinemia on usual biology. The main mechanism is the coagulation factor leak, side effect of the nephrotic syndrom, notably because of the antithrombin III.

Topics: Adult; Aged; Antithrombin III; Delayed Diagnosis; Drug Therapy, Combination; Echocardiography, Doppler; Fatal Outcome; Female; Humans; Kidney Function Tests; Male; Middle Aged; Morpholines; Nephrotic Syndrome; Prednisone; Proteinuria; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thrombosis

Oral anticoagulation (OAC) with coumarins and new anticoagulants are highly effective in preventing thromboembolic complications. However, some studies indicate that over- and under-treatment with anticoagulants are fairly common. The aim of this paper is to assess the appropriateness of treatment in patients with a long-term indication for OAC, and to describe the corresponding characteristics of such patients on the basis of screening results from the cluster randomized PICANT trial.. Randomly selected family practices in the federal state of Hesse, Germany, were visited by study team members. Eligible patients were screened using an anonymous patient list that was generated by the general practitioners' software according to predefined instructions. A documentation sheet was filled in for all screened patients. Eligible patients were classified into 3 categories (1: patients with a long-term indication for OAC and taking anticoagulants, 2: patients with a long-term indication for OAC but not taking anticoagulants, 3: patients without a long-term indication for OAC but taking an anticoagulant on a permanent basis). IBM SPSS Statistics 20 was used for descriptive statistical analysis.. We screened 2,036 randomly selected, potentially eligible patients from 52 family practices. 275 patients could not be assigned to one of the 3 categories and were therefore not considered for analysis. The final study sample comprised 1,761 screened patients, 1,641 of whom belonged to category 1, 78 to category 2, and 42 to category 3. INR values were available for 1,504 patients of whom 1,013 presented INR values within their therapeutic ranges. The majority of screened patients had very good compliance, as assessed by the general practitioner. New antithrombotic drugs were prescribed in 6.1% of cases.. The screening results showed that a high proportion of patients were receiving appropriate anticoagulation therapy. The numbers of patients with a long-term indication for OAC therapy that were not receiving oral anticoagulants, and without a long-term indication that were receiving OAC, were considerably lower than expected. Most patients take coumarins, and the quality of OAC control is reasonably high.. Current Controlled Trials ISRCTN41847489.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Coumarins; Dabigatran; Family Practice; Female; Germany; Guideline Adherence; Heart Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Mass Screening; Middle Aged; Morpholines; Practice Guidelines as Topic; Process Assessment, Health Care; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Thrombosis; Venous Thromboembolism

The article discusses various options of anticoagulant therapy for pulmonary thromboembolism and the main criteria of medication choice including the use of unfractionated heparin, low-molecular-weight heparins, and rivaroxaban. The data presented are based on the own experience and results of international clinical trials.

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Outcome Assessment, Health Care; Patient Selection; Pulmonary Embolism; Risk Adjustment; Rivaroxaban; Thiophenes

Thromboembolic disease (TD) is a relatively common disease with acute risk of death and potential long-term consequences in term of postthrombotic syndrome or chronic pulmonary hypertension. Anticoagulant therapy is the basic therapeutic procedure; thrombolytic therapy and the introduction cava filter are appropriately indicated for individual cases. In past few years, new direct oral anticoagulant drugs (NOAC) have occurred - Xa factor or thrombin inhibitors which have demonstrated the same efficacy and even higher safety in comparison to conventional treatment. In mid 2014, 3 drugs of this group are registered in Czech Republic - rivaroxaban (Xarelto®), dabigatran (Pradaxa®) and apixaban (Eliquis®). These drugs have comparable efficacy and safety but they differ in schedule of dose administration. Rivaroxaban and apixaban can be administered immediately after diagnosis of venous thrombosis or hemodynamically stable pulmonary embolism. LMWH application has to precede few days the administration of dabigatran. Limitation of new drugs is their price. Unavailability of antidotes is temporary because current researches continue to find one for dabigatran and another for both of xabans. Duration of anticoagulant treatment after acute phase depends on the presence of thrombosis risk factors and the individual bleeding risk. Minimal duration of anticoagulant therapy is 3 months, commonly 6-12 months and in high risk patients it is "long term" treatment. Good results of new anticoagulant drugs in trials in term of thromboembolism recurrence prevention may change established habits in TD patients with long term treatment.

Topics: Administration, Oral; Aged; Antithrombins; Benzimidazoles; beta-Alanine; Czech Republic; Dabigatran; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; Venous Thrombosis

Topics: Administration, Oral; Cardiology; Congresses as Topic; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin; Hospitalization; Humans; Infusions, Intravenous; Length of Stay; Morpholines; Pulmonary Embolism; Rivaroxaban; Societies, Medical; Thiophenes

Pulmonary embolism is a leading cause of fatality in elective orthopaedics. Recently introduced oral thromboprophylaxis (rivaroxaban) has a logistic advantage but has also raised early concerns amongst arthroplasty surgeons. The aim of this study was to evaluate the impact of rivaroxaban as a chemical thromboprophylaxis following knee arthroplasty in reference to radiologically diagnosed PE and return to theatre following wound complication.. Following the introduction of new NICE guidelines in our institute 266 consecutive TKR receiving rivaroxaban were studied prospectively and compared with retrospectively collected consecutive 596 TKR prior to adoption of the guidelines. Both of these groups were studied for radiologically diagnosed symptomatic VTE episodes within 90days and return to theatre following wound complication.. A total of 862 cases were studied, out of which 596 were in the retrospective control group and 266 were in the prospective rivaroxaban group. Both the groups had a female predominance with a mean age at the time of surgery as 68 and 69 in control and prospective cohort respectively. There were 24 radiologically diagnosed symptomatic PE and one DVT in the control group whereas, the rivaroxaban prospective group had 2 PE and 2 DVT cases. The return to theatre following wound complication was 2 and 7 in control and prospective group respectively.. Following the introduction of rivaroxaban the number of symptomatic radiologically confirmed PE events declined (p=0.0084) but the return to theatre rate due to wound complications increased (p=0.0049).. III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Case-Control Studies; Female; Follow-Up Studies; Humans; Middle Aged; Morpholines; Postoperative Complications; Primary Prevention; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Rivaroxaban; Survival Rate; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Topics: Adult; Anticoagulants; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Treatment Outcome

As of September 2013, three new oral anticoagulants (NOACs) are now available for clinical use on the Pharmaceutical Benefits Scheme in Australia. All three are for stroke prevention in atrial fibrillation, and one will also be available for the treatment of deep venous thrombosis and pulmonary embolism. All have been evaluated in large, multicentre randomised clinical trials. These drugs show at least equivalent efficacy to the current standard of care, the vitamin K antagonist warfarin. Major bleeding rates are overall comparable with warfarin, but there is an important reduction in intracranial bleeding of approximately 50% with all NOAC agents. The NOACs are administered in a simple, fixed dose regimen. There are a few clinically important interactions with other medications or diet. Concerns exist about the potential for irreversible bleeding in the small number of patients in which that occurs. This short report will discuss the pharmacology of these agents, the indications for use, aspects of laboratory monitoring and the management of bleeding with these agents.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Australia; Benzimidazoles; beta-Alanine; Dabigatran; Emergency Service, Hospital; Humans; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thrombosis

To report 2 cases in which point-of-care international normalized ratios (POC-INRs) measured using a Hemochron Jr. Signature Elite device (International Technidyne Corporation) were inaccurate in rivaroxaban-treated patients.. Therapy in an 86-year-old man with atrial fibrillation was converted from warfarin to rivaroxaban 15 mg twice daily because of a deep venous thrombotic event despite an INR of 2.4, which was within the therapeutic range. One week later a POC-INR was inadvertently measured, which was 6.3. In light of the POC-INR being markedly elevated, a laboratory test for INR was performed, which gave a result of 2.74. Therapy in a 66-year-old man was converted from war-farin to rivaroxaban 15 mg twice daily because of unstable INRs and a pulmonary embolism despite a therapeutic INR. Seven days after rivaroxaban was started, the patient's POC-INR was 9.2; simultaneously measured laboratory-determined INR was 2.0. For both patients, coagulation tests performed on follow-up visits revealed continued discordance between the POC and laboratory assays.. Rivaroxaban is an oral factor Xa inhibitor with a predictable pharmacokinetic profile, allowing for a fixed-dose regimen without the need for coagulation monitoring. When patients' therapy is switched from rivaroxaban to warfarin, it is recommended that the drugs be given concurrently until the INR is 2.0 or higher, to ensure adequate anticoagulation during this well-recognized vulnerable period for stroke. POC testing is a common method of INR assessment in clinical practice. During ROCKET-AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), POC-INRs were measured exclusively with the INRatio device (Hemosense), and values above 4 were seen very rarely (0.25%), which indicates that the values determined in our patients were highly unusual.. Our 2 patients receiving rivaroxaban had POC-INRs elevated beyond what was expected; these measurements were discordant from INRs simultaneously measured via the laboratory. A prospective evaluation assessing the accuracy of other commonly used POC-INR devices in patients receiving rivaroxaban would determine whether our findings extend to other devices. Until that time, laboratory measurement of INR or POC-INR using an INRatio device is recommended when patients' therapy is transitioned from rivaroxaban to warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Male; Morpholines; Point-of-Care Systems; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thrombosis

The introduction of the new oral anticoagulant drugs (NOACs) has recently been paid much attention. The main advantage of these drugs is that routine monitoring of the anticoagulant effects does not seem necessary.. A 53-year-old man who had just undergone partial knee arthroplasty went to the emergency department with shortness of breath and respiratory chest pain. The symptoms arose the day after thromboprophylaxis was switched from dalteparin 5000 IU QD to rivaroxaban 10 mg QD. The patient also used carbamazepine 600 mg BID for epilepsy. Based on a CT scan the patient was diagnosed with pulmonary embolisms. Use of carbamazepine, a CYP3A4 inducer, probably led to an increased clearance of rivaroxaban resulting in pulmonary embolisms.. We encourage monitoring of the anticoagulant effects of NOACs in case of drug-drug interactions, especially when NOACs are given in higher doses for a long period, in order to prevent treatment complications.

Topics: Anticoagulants; Anticonvulsants; Arthroplasty, Replacement, Knee; Carbamazepine; Drug Interactions; Epilepsy; Humans; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes

No tangible advantage over heparin therapy followed by a vitamin K antagonist, in an unblinded trial.

Topics: Anticoagulants; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes

Topics: Anticoagulants; Drug Administration Schedule; Humans; Morpholines; Practice Guidelines as Topic; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes

Thromboprophylaxis for deep vein thrombosis (DVT) after lower-extremity trauma could include rivaroxaban, an oral medication that does not need laboratory monitoring.. To assess rivaroxaban's efficacy in preventing DVTs after pelvic trauma compared to its historical incidence.. All patients admitted with pelvic fractures in a 12-month period followed a standardized thromboprophylaxis protocol: 1) rivaroxaban 10 mg/day within 24 h of injury or upon hemodynamic stability; 2) pre-operative, post-operative, and 30-day extremity ultrasound; 3) ventilation-perfusion scintigraphy for clinical signs of pulmonary embolus; and 4) a 45-, 90-, and 120-day re-evaluation. Rivaroxaban administration ceased the day of surgery and restarted 12 h post-operatively or upon hemodynamic stability, continuing for 30 days. Excluded patients had severe neurological or hepatosplenic injuries, heparin hypersensitivity, or hemodynamic instability.. Of 113 patients assessed, 84 patients (66 males), average age 46.6 years (range 19-69 years), were included. They had isolated pelvic trauma (n = 37), associated lower limb injuries (n = 47), average Injury Severity Score 21.4 (range 16-50), and average Glasgow Coma Scale score 13.6 (range 9-15). Patients receiving thromboprophylaxis soon after their fracture (n = 64) had a lower incidence of DVT than those receiving delayed thromboprophylaxis (n = 20) (p = 0.02). One patient (1.2%) died from a pulmonary embolus; 13 had asymptomatic below-the-knee DVTs. Rivaroxaban did not increase intra- or post-operative bleeding in surgical wounds.. DVT incidence after pelvic fractures is reduced by administering antithrombotics within 24 h of injury or, if the patient is hemodynamically unstable, 24 h after stabilization. Rivaroxaban is a safe and effective method of providing this thromboprophylaxis.

Topics: Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Fractures, Bone; Glasgow Coma Scale; Humans; Injury Severity Score; Lower Extremity; Male; Middle Aged; Morpholines; Pelvic Bones; Pulmonary Embolism; Radionuclide Imaging; Rivaroxaban; Thiophenes; Time Factors; Ultrasonography; Venous Thrombosis; Young Adult

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Interactions; Humans; Morpholines; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes

Topics: Anticoagulants; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thrombosis

Topics: Acute Disease; Anticoagulants; Evidence-Based Medicine; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Topics: Anticoagulants; Humans; Morpholines; Pneumococcal Vaccines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thrombosis

Rivaroxaban is a direct oral anticoagulant targeting factor Xa. Efficacy and safety of rivaroxaban were evaluated through the phase 3 EINSTEIN program, consisting in three clinical trials regarding the treatment of deep vein thrombosis (EINSTEIN DVT), pulmonary embolism (EINSTEIN PE), and in secondary prevention after a first episode of venous thromboembolic disease (EISNTEIN EXT). Rivaroxaban was recently approved both by the European and the French Health agencies for the treatment of DVT and prevention of deep vein thrombosis recurrence. This report addresses the use of rivaroxaban in clinical practice in such indications.

Topics: Age Factors; Anticoagulants; Drug Interactions; Factor Xa; France; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamins

Due to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement.. Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources.. 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%.. Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of 547,422 Euro over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to 270,068 Euro.. According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxis.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Budgets; Cost Control; Dabigatran; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Morpholines; Polysaccharides; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Spain; State Medicine; Thiophenes; Venous Thromboembolism

Topics: Acute Disease; Administration, Oral; Anticoagulants; Enoxaparin; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Recurrence; Risk Assessment; Rivaroxaban; Thiophenes; Venous Thrombosis

Clinical data on the risk factors, incidence, consequences and current treatment options of venous thromboembolism are reviewed. Current guidelines advise anticoagulant treatment for a few weeks or months in immobilized patients treated in hospital, and after major surgery. The initial treatment is based on heparin, followed by vitamin K antagonist treatment. Recently a number of new, partially orally administered medications have undergone clinical investigations and based on the results three of them were also registered for the prevention and treatment of venous thromboembolism. Direct thrombin inhibitors, direct and indirect Factor Xa inhibitors exhibited proven non-inferiority or superiority compared with traditional treatment options. The superior efficacy or non-inferiority was not accompanied with an increase in the bleeding risk. Results of the most important clinical trials are reviewed. Based on these results, prevention and treatment of venous thromboembolism will change substantially in the near future.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Drug Costs; Drugs, Investigational; Factor Xa Inhibitors; Humans; Hungary; Morpholines; Oligosaccharides; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Thrombin; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Drug Approval; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; United States; United States Food and Drug Administration; Venous Thrombosis

Amongst numerous promising anticoagulant molecules, rivaroxaban (Xarelto(®)), dabigatran (Pradaxa(®)) and apixaban (Eliquis(®)) have been registered outside the USA in the prevention of thromboembolic events in patients undergoing total hip or knee prosthetic replacement. Rivaroxaban however has been granted authorisation by the FDA for the thromboprophylaxis after surgery for total hip or knee surgery. Dabigatran has been granted authorisation by the FDA in non-valvular atrial fibrillation (RE-LY trial) while rivaroxaban is expecting approval in this same indication (ROCKET trial). Phase III results in the treatment and in the secondary prevention of established venous thrombosis and pulmonary embolism are encouraging. These small molecules are obtained by chemical synthesis, their molecular weight is lower than 500 daltons. Many coagulation tests may be affected by these molecules. Those modifications should be known in order to avoid misinterpretation of the tests but could also be used to measure plasma concentrations of these products. The choice of a non specific global and readily available test has been documented (Quick time for rivaroxaban and aPTT for dabigatran). Anti-Xa (for rivaroxaban) and anti-IIa (for dabigatran) activities should however be preferred, expressed in ng/ml with calibrated plasmas (containing predetermined concentration of the tested drug). The half-life is around 8 to 12 hours, with a peak activity 2 to 4 hours after ingestion. Dabigatran is mainly eliminated via the kidney, hence requiring dose-adjustment in case of moderate renal insufficiency, and contra-indicated in case of severe renal insufficiency. Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. No data are available in pregnancy or pediatrics, clinical trials are ongoing. There are few interactions with concomitant drugs, which should not be ignored. The short half-life of these new agents compensates for the lack of any specific antidote in many instances. Their oral administration, without the need for dose adjustment, and without requirement for a laboratory monitoring will increase their use in a large number of patients, in those indications for which an approval has been granted by health authorities.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Contraindications; Dabigatran; Drug Approval; Humans; Kidney; Liver; Morpholines; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; United States; United States Food and Drug Administration

Following the landmark study by Barritt and Jordan in 1960, in which patients with venous thromboembolism (VTE) were randomized to no treatment or a combination of heparin and warfarin, antithrombotic therapy for this disease became widely accepted. This study was stopped prematurely because half of the non-treated patients had recurrent pulmonary embolism (PE), or died. It was subsequently found that after a VTE, patients given warfarin alone had a 3-4-fold higher incidence of recurrent VTE than patients given both heparin and warfarin. Since the 1990 s, standard therapy for VTE has comprised an initial 5-7 day course of parenteral anticoagulant plus warfarin continued for at least 3 months. Recently, several orally active small molecules have been evaluated in the treatment of VTE, including a direct thrombin inhibitor and direct Factor Xa inhibitors. Other novel oral agents are also in development for VTE treatment. Although the DTI ximelagatran, the first oral agent to be introduced since warfarin was withdrawn from the market in Europe because of hepatotoxicity, evidence from clinical trial evaluating other single target-specific oral agents in the treatment of VTE is encouraging. It is therefore likely that use of warfarin in the treatment and secondary prevention of VTE will decrease should these novel oral agents be introduced for these indications. Additionally, there will be less distinction between initial and long-term therapy, and a great majority of patients will be treated on an outpatient basis for prolonged periods of time. Recently these expectations were fulfilled by the results of two Phase III studies in patients with VTE. The Recover I study indicated that Dabigatran (150 mg b.d.) following an initial course of LMWH was non-inferior to the standard treatment of LMWH plus warfarin, with also a similar safety profile. The Einstein DVT study revealed that Rivaroxaban as a single agent can safely replace the standard treatment in patients with DVT. Taken together these studies and a few others that have or are about to be completed will indeed introduce a paradigm shift in the way patients with VTE will be treated.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thrombosis; Warfarin

Warfarin and heparin are the traditional mainstay anticoagulant therapies for treating thromboembolic disease. These drugs, with a documented history of utility, also have inherent difficulties in usage; in particular, the complicated monitoring and numerous drug-drug interactions of warfarin, and the need for parenteral administration of heparins. New agents have recently emerged that target specific elements of the clotting pathway. Rivaroxaban, which inhibits activated factor X (Xa), is currently in clinical trials and is the most advanced factor Xa inhibitor. The drug offers once-daily oral dosing, with no need for injections, dose titration, or frequent blood tests to monitor the international normalised ratio. It has a rapid onset of action and, although there is no specific antidote, it has a short plasma elimination half-life (about 5-9 hours). Evidence from recently published large-scale phase III clinical trials shows rivaroxaban to be superior to enoxaparin for prophylaxis of venous thromboembolism after major orthopaedic surgery. Studies have shown rivaroxaban to have a sound safety profile, with an incidence of bleeding similar to enoxaparin in phase III clinical trials. Few side effects and drug-drug interactions between rivaroxaban and common medications have been found thus far, although some interactions with potent cytochrome P450 3A4 inhibitors have been observed. It is hoped that rivaroxaban may be used as a first-line anticoagulant for prophylaxis of venous thromboembolic disease in postsurgical patients.

Topics: Administration, Oral; Anticoagulants; Drug Interactions; Factor Xa Inhibitors; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Pulmonary Embolism; Research Design; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Risk; Rivaroxaban; Thiophenes; Venous Thromboembolism