rivaroxaban and Venous-Thrombosis

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

Isolated distal deep vein thrombosis (IDDVT) is a frequent manifestation of venous thromboembolism (VTE), accounting for up to 50% cases of lower‑extremity deep vein thrombosis (DVT). As compared with proximal DVT, IDDVT is more frequently associated with transient risk factors and less often occurs unprovoked or in the presence of permanent risk factors. IDDVT generally carries a significantly lower risk of proximal extension, post‑thrombotic syndrome, and recurrence than proximal DVT. Nevertheless, some patient subgroups, such as those with active cancer, other predisposing permanent risk factors, prior VTE, unprovoked IDDVT, persistently restricted mobility, and trifurcation or bilateral involvement, exhibit a non‑negligible recurrence risk. Unlike in proximal DVT, the optimal therapeutic management of IDDVT remains uncertain. In clinical practice, the vast majority of IDDVT patients are managed with anticoagulation rather than with surveillance serial compression ultrasonography, which tends to be reserved to individuals at a high bleeding risk. Available data seem to favor anticoagulant therapy over no anticoagulation, thanks to a significant reduction in the risk for proximal extension and recurrence, without increased bleeding risk. Recent results of the RIDTS (Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis) randomized clinical trial with rivaroxaban further support the use of anticoagulant therapy for 3 months over shorter durations (eg, ≤6 weeks). In this review, we offer an updated overview of the epidemiology, risk factors, and clinical course of IDDVT, with a focus on the therapeutic management in light of current guideline recommendations and most recent evidence. We also present real‑life clinical cases of IDDVT with proposed therapeutic approaches, and highlight major challenges and gaps in this field.

Topics: Anticoagulants; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US).. We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin.. Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs.. This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Retrospective Studies; Rivaroxaban; Stroke; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

The primary aim of this network meta-analysis (NMA) is to compare the incidence of venous thromboembolisms (VTE) and bleeding risk following the use of pharmacological and non-pharmacological thromboprophylaxis for arthroscopic knee surgery (AKS). This study assumed the null hypothesis which was that there will be no difference in the incidence of VTE and bleeding risk when comparing no treatment, pharmacological treatment, and non-pharmacological treatment for preventing VTE events following AKS.. A systematic electronic search of CENTRAL, Medline, Embase, and ClinicalTrials.gov was carried out. All English language prospective randomized clinical trials published from date of database inception to November 21, 2021 were eligible for inclusion. All papers addressing arthroscopic knee surgery were eligible for inclusion regardless of timing of surgery, operation, surgical technique, or rehabilitation. Multiple random effects NMAs were conducted to compare all treatments for each outcome. The primary outcome was the incidence of pulmonary embolism (PE) and secondary outcomes consisted of overall deep vein thrombosis (DVT), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Adverse outcomes consisted of major and minor bleeding, as well as adverse events.. A total of nine studies with 4526 patients were included for analysis. There were 1054 patients in the no treatment/placebo group (NT/Placebo), 1646 patients in the graduated compression stockings, 810 patients in the extended-duration (> 10 days) low molecular weight heparin (Ext-LMWH) group, 650 patients in the short-duration (< 10 days) LMWH group (Short-LMWH), and 356 patients in the rivaroxaban group. GCS, Ext-LMWH, Short-LMWH and rivaroxaban all demonstrated low risks of PE, symptomatic DVT, asymptomatic DVT, combined DVT and all-cause mortality. Similarly, all interventions demonstrated a low risk of major bleeding.. There is no significant difference in the risk reduction of PEs, symptomatic DVTs, major/minor bleeding, and/or all-cause mortality when using LWMH (including short or extended regimens), rivaroxaban, graduated compression stockings or no treatment following arthroscopic knee surgery. Future primary research on the efficacy of thromboprophylaxis following arthroscopic knee surgery should stratify outcomes based on key patient (i.e., age, sex, comorbidities) and surgical (i.e., major vs. minor surgery) characteristics and should include acetylsalicylic acid as an intervention.. I, network meta-analysis of Level I studies.

Topics: Anticoagulants; Arthroscopy; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Prospective Studies; Risk Assessment; Rivaroxaban; 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

Lower limb trauma requiring immobilization is a significant contributor to overall venous thromboembolism (VTE) burden. The clinical effectiveness of thromboprophylaxis for this indication and the optimal agent strategy are still a matter of debate. Our main objective was to assess the efficacy of pharmacological thromboprophylaxis to prevent VTE in patients with isolated temporary lower limb immobilization after trauma. We aimed to estimate and compare the clinical efficacy and the safety of the different thromboprophylactic treatments to determine the best strategy.. We conducted a systematic review and a Bayesian network meta-analysis (NMA) including all available randomized trials comparing a pharmacological thromboprophylactic treatment to placebo or to no treatment in patients with leg immobilization after trauma. We searched Medline, Embase, and Web of Science until July 2021. Only RCT or observational studies with analysis of confounding factors including adult patients requiring temporary immobilization for an isolated lower limb injury treated conservatively or surgically and assessing pharmacological thromboprophylactic agents or placebo or no treatment were eligible for inclusion. The primary endpoint was the incidence of major VTE (proximal deep vein thrombosis, symptomatic VTE, and pulmonary embolism-related death). We extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses for NMA and appraised selected trials with the Cochrane review handbook. Fourteen studies were included (8,198 patients). Compared to the control group, rivaroxaban, fondaparinux, and low molecular weight heparins were associated with a significant risk reduction of major VTE with an odds ratio of 0.02 (95% credible interval (CrI) 0.00 to 0.19), 0.22 (95% CrI 0.06 to 0.65), and 0.32 (95% CrI 0.15 to 0.56), respectively. No increase of the major bleeding risk was observed with either treatment. Rivaroxaban has the highest likelihood of being ranked top in terms of efficacy and net clinical benefit. The main limitation is that the network had as many indirect comparisons as direct comparisons.. This NMA confirms the favorable benefit/risk ratio of thromboprophylaxis for patients with leg immobilization after trauma with the highest level of evidence for rivaroxaban.. PROSPERO CRD42021257669.

Topics: Adult; Anticoagulants; Bayes Theorem; Humans; Leg; Lower Extremity; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Despite the usefulness of traditional Chinese medicine (TCM) in the treatment of lower deep vein thrombosis (DVT), there is no consensus on safety and efficacy. We aim to systematically evaluate the safety and efficacy of TCM combined with Rivaroxaban in the treatment of lower limb DVT.. An online search of databases such as Cochrane Library, Embase, Pubmed, and Web of science, as well as CBM, China Science and Technology Journal Database, China Knowledge Network (CNKI) and Wanfang Data (from inception to July, 2021) was performed. All published clinical randomized controlled trials (RCTs) were screened manually, evaluated for quality and considered for meta-analysis using RevMan 5.3.. Nine RCTs with a total of 730 cases were included, 368 cases in the trial group were treated with TCM combined with Rivaroxaban, and 362 cases in the control group were treated with Rivaroxaban alone after surgery. Clinical efficiency was significantly higher in the test group [OR = 3.33, 95% CI (2.01, 5.53), P < .00001], the circumference of the affected limb was significantly lower in the thigh and calf, respectively [MD = -1.48, 95% CI (-1.88, -1.09), P < .00001], [MD = -0.54, 95% CI (-0.62, -0.46), P < .00001], pain scores were significantly lower [MD = -0.97, 95% CI (-1.58, -0.36), P = .002], coagulation index plasma fibrinogen (FIB) was significantly lower [MD = -0.85, 95% CI (-1.18, -0.52), P < .00001], coagulation function index D-2 aggregates were significantly reduced [MD = -0.69, 95% CI (-1.13, -0.24), P = .002], serum hypersensitive C-reactive protein (hs-CRP) measurements were significantly reduced [MD = -5.37, 95% CI (-9.20, -1.55), P = .006], complications measurement was significantly lower [OR = 0.60, 95% CI (0.27, 1.30), P = .20], activated partial thrombin time (ATPP) measurement was significantly lower [MD = 5.70, 95% CI (4.28, 7.12), P < .00001] and prothrombin time (PT) measurement was significantly lower [MD = 1.64, 95% CI (0.70, 2.57), P = .0006].. Based on the available evidence, TCM combined with Rivaroxaban for treating lower extremity DVT have better clinical efficacy and safety profile, reducing the risk of bleeding complications and adverse effects. Further improved studies are needed to support this inference.

Topics: C-Reactive Protein; Drugs, Chinese Herbal; Fibrinogen; Humans; Lower Extremity; Medicine, Chinese Traditional; Rivaroxaban; Venous Thrombosis

Cardiovascular disease (CVD) remains the leading cause of death in the USA. Several risk factors have been identified, and obesity has become one of prominent concern. Excessive weight is considered a risk factor for CVD based on evidence linking it to a hypercoagulable state. Considering the prevalence of CVD and obesity in the USA, along with the increased risk for thrombus-related events, anticoagulation plays a significant role in prevention and treatment. Direct oral anticoagulants have taken the place of many traditional anticoagulants. Considering the recently approved indications and continued postmarketing studies conducted with rivaroxaban, this updated review provides data on the overall impact of obesity on this compound. This includes data obtained from both healthy obese volunteers and obese patients with various CVD conditions enrolled in rivaroxaban clinical trials, along with data obtained from postmarketing real-world evidence studies. Assessment of the clinical pharmacology and population pharmacokinetics in obese individuals revealed no clinically relevant effects of increased weight. Additionally, subgroup analyses from each of the pivotal phase III trials supporting the current approved labeling also demonstrated consistent efficacy and safety results in obese patients. Lastly, these findings are further supported by several recent real-world evidence studies assessing the continued effectiveness and safety of rivaroxaban. In conclusion, rivaroxaban's overall pharmacological and clinical profile remained consistent in obese adults when assessed in both drug development and postmarketing studies, supporting the premise that higher weight does not necessitate adjustment in either dose strength or regimen.

Topics: Anticoagulants; Area Under Curve; Body Weight; Cardiovascular Diseases; Humans; Metabolic Clearance Rate; Obesity; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Venous Thrombosis

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

The main purpose of prescribing oral anticoagulants in patients undergoing total knee and total hip replacement surgery is to prevent venous thromboembolism (VTE). The present study aimed to summarize evidence from economic evaluations regarding new oral anticoagulants (NOACs) used in VTE prophylaxis after joint replacement surgery.. To obtain relevant literature on economic evaluations of NOACs used in the prevention of VTE following joint replacement surgery, we searched the Cochrane Library, PubMed, Web of Science, Embase, and Scopus, as well as specialized economic evaluation databases, for articles published from January 2008 to December 2019. Next, 2 reviewers screened the titles and abstracts of studies, extracted data from the full-text articles, and assessed the quality of the methodologies using the Quality of Health Economic Studies checklist.. Twenty-eight studies of economic evaluations met the inclusion criteria of the research. The quality assessment showed that 20 articles had scores within the range of 75 to 100 (high quality), and 9 studies had scores within the range of 50 to 74 (moderate quality). All of the identified studies had been carried out based on modelling, and 23 studies used decision trees to model acute events after surgery. In addition, 20 studies utilized a Markov model to capture long-term complications of VTE. The results showed that rivaroxaban was more cost-effective than apixaban and dabigatran from a perspective of the health care system in the prevention of VTE after total knee and total hip replacement surgery. In addition, apixaban was associated with a lower risk for bleeding events than other NOACs, making it the most cost-effective NOAC from the perspective of the payer.. The results suggest that NOACs are cost-effective alternatives to low-molecular-weight heparins. Rivaroxaban and dabigatran were assessed as the most and least cost-effective prophylaxis options, respectively, after joint replacement surgery for the prevention of VTE. It is recommended that future research be conducted on economic evaluations of edoxaban.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Cost-Benefit Analysis; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Cytomegalovirus is a viral genus of the overarching family Herpesviridae, and is of particular importance because of its relevance to human disease. This association is predominantly due to human cytomegalovirus, a well-studied pathogen. In addition to the mononucleosis syndrome that can occur during acute cytomegalovirus viraemia, this virion has been recurrently implicated as a provoking factor for thromboembolic disease in the published scientific literature. As physicians increasingly forgo extensive laboratory investigation in the setting of clinical hypercoagulability, it has also become evident that in some circumstances whether or not a particular investigation alters clinical management is not necessarily the only important question. Viraemia as a provoking factor for thrombosis stands as such an example. The aim of this Grand Round is to further explore the role of cytomegalovirus as it pertains to thromboembolic disease, especially in the present era of viral-associated thromboembolism.

Topics: Abdominal Pain; Acute Disease; Adult; Anticoagulants; Cytomegalovirus Infections; Factor Xa Inhibitors; Female; Fever; Heparin; Herpesvirus 4, Human; Humans; Lymphocytosis; Mesenteric Vascular Occlusion; Mesenteric Veins; Rivaroxaban; Venous Thrombosis; Viremia

Pregnancy is a known risk factor for spontaneous spinal epidural hematoma. During cesarean section or vaginal delivery, the unstable hemodynamic status that may occur owing to fluctuation of intra-abdominal pressure increases the possibility of spontaneous spinal epidural hematoma. During labor and the postpartum period, neurologic symptoms may be masked by labor pain or anesthesia block, which makes early diagnosis difficult, especially in the obstetric clinic without a neurologist or neurosurgeon.. A 28-year-old woman who had a normal spontaneous delivery under epidural anesthesia developed bilateral lower limb flaccid paralysis and loss of sensation 12.5 hours after delivery. Magnetic resonance imaging showed a 5.2 × 0.9 × 2 cm spinal epidural hematoma with severe spinal cord stenosis at the T2-T5 level with no evidence of a vascular anomaly. After emergent evacuation of the spinal epidural hematoma, lower limb muscle power improved from 0/5 to 1/5, and sensation gradually returned to bilateral lower limbs 22 days postoperatively. Deep vein thrombosis developed at 35 days postoperatively, and an inferior vena cava filter was implanted with urokinase infusion for thrombolytic therapy. She was discharged on day 52 after admission, and lower limb muscle power returned to normal after 3 months.. Clinicians should observe postpartum women for signs of myelopathy or back tenderness and closely monitor neurologic function until anesthesia has run its course. A prompt diagnosis can enable prompt intervention.

Topics: Adult; Analgesia, Epidural; Anesthesia, Epidural; Decompression, Surgical; Delivery, Obstetric; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hematoma, Epidural, Spinal; Humans; Hypesthesia; Laminectomy; Lower Extremity; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Paraplegia; Postoperative Complications; Pregnancy; Puerperal Disorders; Recovery of Function; Rivaroxaban; Spinal Cord Compression; Thrombolytic Therapy; Urokinase-Type Plasminogen Activator; Vena Cava Filters; Venous Thrombosis

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

The role of rivaroxaban in the treatment of leg superficial venous thrombosis (SVT) is uncertain. This article aims to determine if rivaroxaban is an effective and safe treatment for leg SVT. Patients with symptomatic leg SVT of at least 5 cm length were randomized to 45 days of rivaroxaban 10 mg daily or to placebo, and followed for a total of 90 days. Treatment failure (required a nonstudy anticoagulant; had proximal deep vein thrombosis or pulmonary embolism; or had surgery for SVT) at 90 days was the primary efficacy outcome. Secondary efficacy outcomes included leg pain severity, and venous disease-specific and general health-related quality of life over 90 days. Major bleeding at 90 days was the primary safety outcome. Poor enrollment led to the trial being stopped after 85 of the planned 600 patients were randomized to rivaroxaban (

Topics: Adult; Aged; Aged, 80 and over; Factor Xa Inhibitors; Female; Humans; Leg; Male; Middle Aged; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thrombosis; Young Adult

Venous thromboembolism is becoming increasingly recognized as a significant cause of morbidity and mortality in the hospitalized pediatric population. However, young healthy athletes can present with unique risk factors for deep vein thrombosis (DVT) that can be overlooked. Here we report a case of an adolescent male with no inherited risk factors or prior history of DVTs who developed a right femoral vein DVT in the context of playing catcher in baseball after recovering from a bout of streptococcal pharyngitis. We review the evidence that suggests that repetitive squatting-induced compression of the femoral vein can cause the venous stasis and endothelial microtrauma that contributed to the formation of this thrombus.

Topics: Adolescent; Athletes; Baseball; Factor Xa Inhibitors; Humans; Male; Pharyngitis; Rivaroxaban; Streptococcal Infections; Venous Thrombosis

Recent advances in our understanding of the contribution of thrombin generation to arterial thrombosis and the role of platelets in venous thrombosis have prompted new treatment paradigms. Nonetheless, bleeding remains the major side effect of such treatments spurring the quest for new antithrombotic regimens with better benefit-risk profiles and for safer anticoagulants for existing and new indications. The aims of this article are to review the results of recent trials aimed at enhancing the benefit-risk profile of antithrombotic therapy and explain how these findings are changing our approach to the management of arterial and venous thrombosis. Focusing on these 2 aspects of thrombosis management, this article discusses 4 advances: (1) the observation that in some indications, lowering the dose of some direct oral anticoagulants reduces the risk of bleeding without compromising efficacy, (2) the recognition that aspirin is not only effective for secondary prevention of atherothrombosis but also for prevention of venous thromboembolism, (3) the finding that dual pathway inhibition with the combination of low-dose rivaroxaban to attenuate thrombin generation plus aspirin to reduce thromboxane A2-mediated platelet activation is superior to aspirin or rivaroxaban alone for prevention of atherothrombosis in patients with coronary or peripheral artery disease, and (4) the development of inhibitors of factor XI or XII as potentially safer anticoagulants.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Clinical Trials as Topic; Coronary Disease; Drug Therapy, Combination; Factor Xa Inhibitors; Factor XI; Factor XII; Hemorrhage; Humans; Peripheral Arterial Disease; Plaque, Atherosclerotic; Platelet Aggregation; Platelet Aggregation Inhibitors; Primary Prevention; Risk Assessment; Rivaroxaban; Secondary Prevention; Thrombin; Thrombosis; Venous Thrombosis

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

: 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

New oral anticoagulants (NOACs) are likely to have a major impact in the next few years, changing clinical practice of anticoagulation therapy. Evidence on its efficacy and superiority to vitamin K antagonists (VKAs) in treating non-cancer patients have been reported in a few clinical trials. However, patients with cancer are complicated by the prothrombotic nature of the disease, need for potentially invasive surgery and interventions, and altered drug handling. This chapter examines the available evidence and guidelines on the use of NOAC in patients with cancer.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Catheters, Indwelling; Dabigatran; Drug Administration Schedule; Drug Dosage Calculations; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

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 the most widespread severe complication after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We conducted this meta-analysis to further validate the benefits and harms of rivaroxaban use for thromboprophylaxis after THA or TKA. We thoroughly searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Trial sequential analysis (TSA) was applied to test the robustness of our findings and to obtain a more conservative estimation. Of 316 articles screened, nine studies were included. Compared with enoxaparin, rivaroxaban significantly reduced symptomatic VTE (P = 0.0001) and symptomatic deep vein thrombosis (DVT; P = 0.0001) but not symptomatic pulmonary embolism (P = 0.57). Furthermore, rivaroxaban was not associated with an increase in all-cause mortality, clinically relevant non-major bleeding and postoperative wound infection. However, the findings were accompanied by an increase in major bleeding (P = 0.02). The TSA demonstrated that the cumulative z-curve crossed the traditional boundary but not the trial sequential monitoring boundary and did not reach the required information size for major bleeding. Rivaroxaban was more beneficial than enoxaparin for preventing symptomatic DVT but increased the risk of major bleeding. According to the TSA results, more evidence is needed to verify the risk of major bleeding with rivaroxaban.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

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

Hypereosinophilic syndrome (HES) can be fatal, particularly when eosinophils infiltrate vital organs and/or if extensive thrombosis develops. However there are no standard recommendations for the use of anticoagulant therapy of HES in the setting of thrombosis.. We herein present a case of a 46-year-old female who presented with marked peripheral eosinophilia with symptoms of multi-organ infiltration and extensive deep venous thrombosis (DVT). In this case, evaluation was carried out before the diagnosis was established, and timely standard-dose corticosteroids combined with a new oral anticoagulant (NOAC) therapy were carried out.. These measures resulted in a rapid response and long-term disease control.. Although there are no data to support which anticoagulant is preferred in this setting, this case indicates that the new oral anticoagulants may play an important role in the treatment of thrombosis in HES.

Topics: Anti-Inflammatory Agents; Combined Modality Therapy; Factor Xa Inhibitors; Female; Humans; Hypereosinophilic Syndrome; Kidney; Liver; Middle Aged; Platelet Transfusion; Prednisolone; Rivaroxaban; Thorax; Venous 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

As a class, the target-specific oral anticoagulants (TSOACs) are at least as effective as warfarin, often with superior safety for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and the treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. Currently, dabigatran, the direct thrombin inhibitor, along with rivaroxaban and apixaban, direct factor Xa inhibitors, has been approved in multiple countries for these indications. Edoxaban, which has received approval for the abovementioned indications in Japan, has demonstrated efficacy and safety comparable to or better than warfarin in Phase III clinical trials and is under further regulatory consideration. It is anticipated that the use of TSOACs will increase as practitioners and healthcare systems gain familiarity with these drugs and adopt their use into clinical practice. This review will provide a brief overview of the TSOAC Phase III clinical trials for prevention of stroke and systemic embolic events in patients with AF and the Phase III clinical trials for the prevention of recurrent VTE, discuss current treatment guidelines, address how TSOACs may help meet national safety goals, and provide clinical decision-making guidance regarding the use of TSOACs for hospitalists.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa Inhibitors; Hospitalists; Humans; International Normalized Ratio; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thrombosis; Warfarin

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

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

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 1 in 1,000 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 novel oral anticoagulants (NOACs) 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 treatment of DVT.. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the treatment of DVT.. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations.. We included randomised controlled trials in which people with a DVT confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor for the treatment of DVT.. 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 review author (PK). We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and PE. 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 11 randomised controlled trials of 27,945 participants. Three studies tested oral DTIs (two dabigatran and one ximelagatran), while eight tested oral factor Xa inhibitors (four rivaroxaban, two apixaban and two edoxaban). We deemed all included studies to be of high methodological quality and low risk of bias. The quality of the evidence was graded as high as the outcomes were direct and effect estimates were consistent and precise, as reflected in the narrow CIs around the ORs. Meta-analysis of three studies (7596 participants) comparing oral DTIs with standard anticoagulation groups showed no difference in the rate of recurrent VTE (OR 1.09; 95% CI 0.80 to 1.49), recurrent DVT (OR 1.08; 95% CI 0.74 to 1.58), fatal PE (OR 1.00; 95% CI 0.27 to 3.70), non-fatal PE (OR 1.12; 95% CI 0.66 to 1.90) or all-cause mortality (OR 0.82; 95% CI 0.60 to 1.13). However, oral DTIs were associated with reduced bleeding (OR 0.68; 95% CI 0.47 to 0.98). Meta-analysis of eight studies (16,356 participants) comparing oral factor Xa inhibitors with standard anticoagulation demonstrated a similar rate of recurrent VTE between the two treatments (OR 0.89; 95% CI 0.73 to 1.07). Oral factor Xa inhibitors were associated with a lower rate of recurrent DVT (OR 0.75; 95% CI 0.57 to 0.98). However, this was a weak association, heavily dependent on one study. The rate of fatal (OR 1.20; 95% CI 0.71 to 2.03), non-fatal PE (OR 0.94; 95% CI 0.68 to 1.28) and all-cause mortality (OR 0.90; 95% CI 0.65 to 1.23) was similar between the two treatment groups. Oral factor Xa inhibitors were also associated with reduced bleeding (OR 0.57; 95% CI 0.43 to 0.76). None of the included studies measured post-thrombotic syndrome or health-related quality of life.. NOACs such as DTIs and factor Xa inhibitors may be an effective and safe alternative to conventional anticoagulation treatment for acute DVT.

Topics: Administration, Oral; Antithrombins; Azetidines; Benzylamines; Dabigatran; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thrombosis

The decision to prescribe anticoagulant therapy must consider the balance between reducing the risk of thromboembolic events and increasing the risk of bleeding. Although assessments of net clinical outcomes with oral anticoagulants are not new, this article presents an evaluation of benefit-risk by considering only events of substantial and comparable clinical relevance (i.e., events with serious long-term sequelae likely to have irreversible consequences, including death). This is based on the concept of the number of patients who need to be treated to elicit one beneficial [number needed to treat (NNT)] or harmful [number needed to harm (NNH)] event. The approach is illustrated using data from phase III trials of rivaroxaban, selected because it has the broadest range of approved indications of the novel oral anticoagulants. For example, in the ATLAS ACS 2 TIMI 51 trial of rivaroxaban plus standard antiplatelet therapy following an acute coronary syndrome event, the current analysis demonstrates that 63 patients need to be treated (over 24 months) to prevent one all-cause mortality event compared with placebo (NNT = 63). Conversely, 500 patients need to be treated to cause one additional intracranial hemorrhage (NNH = 500). The most relevant and clinically meaningful assessment of benefit-risk may therefore be achieved by focusing only on events of greatest concern to patients and physicians, namely those with (potentially) long-lasting, severe consequences. Although there are clear limitations to this type of analysis, rivaroxaban appears to demonstrate a broadly favorable benefit-risk profile across multiple clinical indications.

Topics: Acute Coronary Syndrome; Factor Xa Inhibitors; Humans; Numbers Needed To Treat; Risk Assessment; Rivaroxaban; Stroke; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

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 aim of this study is to compare effectiveness and safety profile of rivaroxaban with bemiparin in 3-week extended prophylaxis after knee arthroscopy.. Four hundred and sixty-seven patients were included in this review divided in two groups. One followed prophylaxis with rivaroxaban and the other one with bemiparin. All patients were interviewed and explored at 1 and 3 months postoperatively, looking for symptomatic signs of deep-vein thrombosis (DVT). In case of suspicion, diagnostic tests were performed. Collected data were age, sex, gender, diagnosis, time with ischemia, body mass index, concomitant diseases, concomitant therapy, DVT signs, treatment satisfaction, minor and major complications, treatment adherence and tolerability.. No thromboembolic events were observed in any of the groups. In one case treated with rivaroxaban, the drug had to be withdrawn due to epistaxis.. Our study showed that extended prophylaxis with 10 mg of rivaroxaban once daily for 3 weeks resulted as effective as bemiparin in knee arthroscopy thromboprophylaxis.

Topics: Adult; Aged; Arthroscopy; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Knee Joint; Male; Middle Aged; Morpholines; Polypharmacy; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Rivaroxaban; Therapeutic Equipoise; Thiophenes; Thrombophilia; 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

Anticoagulation remains the cornerstone of treatment in patients with deep vein thrombosis (DVT). While parenteral anticoagulants and oral vitamin K antagonists (e.g., warfarin) have been used for many decades, the recent development of novel oral anticoagulants have provided clinicians with an expanding set of therapeutic options for DVT. This review summarizes the pharmacology and clinical trial results of these new oral anticoagulants. Several practical considerations to the use of these oral anticoagulants including issues related to adherence, monitoring, and reversal are also discussed.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Medication Adherence; Morpholines; Patient Selection; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thrombosis

Treatment of acute venous thromboembolism (VTE) in cancer patients is challenging, owing to a high risk of recurrent VTE and bleeding complications. The anticoagulants of choice are low molecular weight heparins (LMWHs), because of a proven higher efficacy than vitamin K antagonists (VKAs) and a similar bleeding profile. The recently introduced new oral anticoagulants (NOACs) have the potential to be alternative options for these patients, as these drugs share practical advantages with LMWH, are administered orally, and had similar efficacy to VKAs but a lower bleeding risk in phase 3 studies in the general VTE population.. A systematic literature search was performed to identify phase 3 trials investigating NOACs for the treatment of VTE. The efficacy outcome was recurrent VTE, and the safety outcome was major and clinically relevant non-major bleeding. Pooled incidence rates and risk ratios (RRs) were calculated for cancer patients and non-cancer patients separately.. Five studies were included, with 19 060 patients, of whom 973 (5.1%) had active cancer. The pooled incidence rates of recurrent VTE were 4.1% (95% confidence interval [CI] 2.6-6.0) in cancer patients treated with NOACs, and 6.1% (95% CI 4.1-8.5) in patients treated with VKAs (RR 0.66, 95% CI 0.38-1.2). The pooled incidence rates of major or non-major clinically relevant bleeding were 15% (95% CI 12-18) in cancer patients treated with NOACs, and 16% (95% CI 9.9-22) in patients treated with VKAs (RR 0.94, 95% CI 0.70-1.3). These results form a solid basis for the initiation of a head-to-head comparison of NOACs with LMWH in cancer patients.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morpholines; Neoplasms; Randomized Controlled Trials as Topic; Recurrence; Risk; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

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

Apixaban and rivaroxaban are oral direct factor Xa (FXa) inhibitors used for VTE prevention after total hip (THA) and total knee arthroplasty (TKA). A meta-analysis of level I studies comparing rivaroxaban 10 mg daily or apixaban 2.5 mg twice daily to enoxaparin for the prevention of VTE after THA or TKA was performed analyzing efficacy and safety outcomes. Seven studies met the inclusion criteria including 24,385 patients. Oral FXa inhibitors were superior to enoxaparin in preventing DVT (p<0.00001). There was no difference in the rate of PE, death, major bleeding, blood transfusion requirement, reoperation for bleeding or postoperative wound infections. Oral FXa inhibitors are superior to enoxaparin in preventing DVT after THA and TKA. There is no difference in the rate of PE, death, or postoperative wound complications.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Anticoagulants; Drug Interactions; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

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

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

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

Three new oral anticoagulant agents were tested versus warfarin in separate, large phase III randomized clinical trials for prevention of any stroke and systemic embolism in atrial fibrillation. Dabigatran, a direct thrombin inhibitor, is at 110 mg bid non-inferior and at 150 mg bid superior to warfarin; rivaroxaban, a factor X inhibitor, is also non-inferior, and apixaban, also a factor X inhibitor, is superior to warfarin on the same efficacy end point. Statistical analysis of subgroups does not suggest, for any of the tested drugs, major differences in relation to different risk levels and history of previous stroke/TIA. This re-appraisal of data was undertaken in search for possible additional information, by considering the absolute differences in efficacy and safety events versus warfarin and the corresponding efficiency and number needed to treat, also with regard to secondary versus primary prevention. By this approach, it appears that for all drugs, equivalence or advantage versus warfarin on the efficacy end point is largely driven by a reduction in hemorrhagic rather than ischemic strokes. Dabigatran shows a balanced effect on ischemic and hemorrhagic strokes, and apixaban is most effective in sparing intracranial bleeding versus warfarin. In secondary prevention, better efficiency is shown by dabigatran 150 and apixaban, versus rivaroxaban, despite the higher proportion of post-stroke/TIA patients (55 %) in the ROCKET AF trial of rivaroxaban seemed to favor better results of this drug in secondary prevention. These and other results of our approach should not be directly translated into clinical practice. They may supply useful suggestions to be subsequently tested in specific trials, although head-to-head comparative studies of the three drugs remain unlikely.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thrombosis

In the last few years, several phase III clinical trials of new drug treatments for deep vein thrombosis (DVT) have been carried out or are about to finish. These drugs have a predictable and reliable pharmacokinetic and pharmacodynamic response and do not require monitoring and are consequently an attractive alternative for the treatment of a high proportion of patients with DVT. Dabigatran, edoxaban and idrabiotaparinux have been developed as an alternative to warfarin, and apixaban and rivaroxaban as one-drug only treatment for this disease, with a 1- or 3-week intensified phase of initial treatment, respectively. So far, the reported results show non-inferior efficacy and safety to warfarin or to conventional treatment. Therefore, the new anticoagulants will be particularly useful in patients with unstable INRs, warfarin incompatible pharmacologic interactions, and in those without access to regular coagulation monitoring.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Biotin; Clinical Trials, Phase III as Topic; Dabigatran; Drug Administration Schedule; Humans; Morpholines; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thrombosis

The past decade has witnessed important advances in the diagnosis and treatment of venous thromboembolism with excellent opportunities to apply evidence-based medicine for many of the steps in the management of the disease. This review discusses the clinical prediction rules that should be used to reduce utilization of imaging diagnosis for deep vein thrombosis or pulmonary embolism and the risk stratification for thrombolytic therapy or outpatient management of pulmonary embolism. The treatment options have increased and include low-molecular-weight heparin (LMWH), intravenous or subcutaneous unfractionated heparin - the latter either monitored or not monitored, fondaparinux and rivaroxaban for the initial phase. Thereafter, vitamin K antagonists (VKAs), LMWH, oral factor Xa or thrombin inhibitors are or will soon become available. The VKAs have been subjected to many randomised trial addressing the initiation, intensity, monitoring and self-management. Extended anticoagulation and the selection for that is finally reviewed.

Topics: Anticoagulants; Antithrombins; Clinical Trials as Topic; Diagnostic Imaging; Disease Management; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Morpholines; Radiography; Risk; Rivaroxaban; Thiophenes; Thrombin; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

A number of novel oral anticoagulants that directly target factor Xa or thrombin have been developed in recent years. Rivaroxaban and apixaban (direct factor Xa inhibitors) and dabigatran etexilate (a direct thrombin inhibitor) have shown considerable promise in large-scale, randomised clinical studies for the management of thromboembolic disorders, and have been approved for clinical use in specific indications. Rivaroxaban is licensed for the prevention of venous thromboembolism in patients undergoing elective hip or knee replacement surgery, the treatment of deep-vein thrombosis and prevention of recurrent venous thromboembolism, and for stroke prevention in patients with non-valvular atrial fibrillation. Based on the clinical trial data for rivaroxaban, feedback on its use in clinical practice and the authors' experience with the use of rivaroxaban, practical guidance for the use of rivaroxaban in special patient populations and specific clinical situations is provided. Although most recommendations are in line with the European summary of product characteristics for the approved indications, additional and, in several areas, different recommendations are given based on review of the literature and the authors' clinical experience.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Loss, Surgical; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Female; Humans; Male; Morpholines; Practice Guidelines as Topic; Pregnancy; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Warfarin

Orally active direct inhibitors of thrombin and factor Xa have now been approved for treatment or prevention of deep vein thrombosis,and stroke associated with atrial fibrillation. The factor Xa inhibitor, rivaroxaban, has shown promising results in the treatment of acute coronary syndrome but is not yet approved for that indication. These agents share a rapid onset and are cleared with half lives of approximately 10 hours. At present there is no approved antidote for either class of anticoagulant, making the treatment of life-threatening bleeding episodes problematic. These agents have fewer drug interactions than warfarin, have a predictable clearance, and hence do not require monitoring. Patients with renal insufficiency have delayed clearance and hence may have elevated levels of the drug leading to increased risk of bleeding.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Half-Life; Hemorrhage; Humans; Metabolic Clearance Rate; Morpholines; Rivaroxaban; Stroke; Thiophenes; Venous 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

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Drug Interactions; Factor Xa Inhibitors; Humans; Morpholines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; 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

Rivaroxaban is a direct inhibitor of factor Xa, a coagulation factor at a critical juncture in the blood coagulation pathway leading to thrombin generation and clot formation. It is selective for human factor Xa, for which it has >10 000-fold greater selectivity than for other biologically relevant serine proteases (half-maximal inhibitory concentration [IC(50)], >20 micromol/L). Rivaroxaban inhibits factor Xa in a concentration-dependent manner (inhibitory constant [K(i)], 0.4 nmol/L) and binds rapidly (kinetic association rate constant [k(on)], 1.7x10(7) mol/L(-1) s(-1)) and reversibly (kinetic dissociation rate constant [k(off)], 5x10(-3) s(-1)). By inhibiting prothrombinase complex-bound (IC(50), 2.1 nmol/L) and clot-associated factor Xa (IC(50), 75 nmol/L), rivaroxaban reduces the thrombin burst during the propagation phase. In animal models of venous and arterial thrombosis, rivaroxaban showed dose-dependent antithrombotic activity. In healthy individuals, rivaroxaban was found to have predictable pharmacokinetics and pharmacodynamics across a 5- to 80-mg total daily dose range, inhibiting factor Xa activity and prolonging plasma clotting time. In phase III clinical trials, rivaroxaban regimens reduced rates of venous thromboembolism in patients after total hip or knee arthroplasty compared with enoxaparin regimens, without significant differences in rates of major bleeding, showing that rivaroxaban has a favorable benefit-to-risk profile.

Topics: Administration, Oral; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

Rivaroxaban is a small-molecule, direct factor Xa inhibitor that is under investigation for the prevention and treatment of venous and arterial thrombosis. To date, oral anticoagulants have been limited largely to vitamin K antagonists. Despite their remarkable benefits, vitamin K antagonists are limited by their narrow therapeutic window, the existence of multiple food and drug interactions, and the need for frequent monitoring and dose-adjustment. Rivaroxaban represents a potentially attractive alternative to warfarin, as it could enable simplified once-daily dosing, requires no therapeutic monitoring, and has a lower potential for drug interactions. At present, the safety and efficacy of rivaroxaban for the prophylaxis and treatment of venous thromboembolism has been evaluated in phase-II and phase-III trials involving over 24,000 patients. Rivaroxaban is also being evaluated for the treatment of pulmonary embolism, secondary prevention after acute coronary syndromes, and the prevention of stroke and non-central nervous system embolism in patients with non-valvular atrial fibrillation. The need for new oral anticoagulants, the development and pharmacology of rivaroxaban, results of completed studies of rivaroxaban, and details of ongoing phase-II and phase-III trials with rivaroxaban are the subjects of this chapter.

Topics: Administration, Oral; Animals; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Animals; Anticoagulants; Disease Models, Animal; Drug Design; Drug Evaluation, Preclinical; Factor Xa Inhibitors; Humans; Intracranial Thrombosis; Macaca fascicularis; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thrombosis

Many years of practical use and intensive scientific research have allowed vitamin K antagonists to become a cornerstone of treatment of internal diseases. Nevertheless, limitations in pharmacokinetics and -dynamics of vitamin K antagonists and the availability of new drugs in regard to a targeted anticoagulation therapy ask for a new review of the situation. Proof of effectiveness for the perioperative prophylaxis of venous thrombosis after hip and knee replacement has already been achieved for the direct thrombin inhibitor dabigatran etexilate as well as for the factor Xa inhibitors rivaroxaban und apixaban compared to low molecular weight heparins. These new drugs are now also investigated in patients with internal diseases. For the long-term application (6 or 12 months) concerning the treatment of venous thrombosis and/or stroke prophylaxis in patients with atrial fibrillation data is already available for the direct thrombin inhibitor dabigatran etexilate. Depending on its dosage its effectiveness in comparison with vitamin K antagonists is equal or even better without disadvantages in safety. However, vitamin K antagonists will remain the standard oral anticoagulation until open questions regarding e.g. insufficient therapy adherence (with termination rates up to 20%) or problems with drug interactions of the new competitive products have been completely answered.

Topics: Anticoagulants; Antithrombin Proteins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thrombosis; Vitamin K

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

Currently, pharmacological thromboprophylaxis is frequently required in patients undergoing surgery, due to the high risk of deep venous thrombosis in the perioperative period. The administration of these anticoagulant agents (in Spain, usually low molecular weight heparins or fondaparinux, and in future, probably also the new oral anticoagulants dabigatran and rivaroxaban) may conflict with regional anesthetic techniques, in which maintaining hemostatic integrity is essential. Therefore, safety protocols have been designed that allow thromboprophylaxis to be administered with optimal effectiveness and anesthetic techniques to be performed with maximal safety; these protocols are based on the drug used, as well as on the dose and time of administration. The present chapter reviews the details related to these issues.

Topics: Acenocoumarol; Administration, Oral; Anesthesia, Conduction; Anticoagulants; Benzimidazoles; Clinical Protocols; Dabigatran; Early Ambulation; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Risk Factors; Rivaroxaban; Safety; Surgical Procedures, Operative; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Rivaroxaban (Xarelto) is a new oral, direct and selective inhibitor of the factor Xa of the coagulation cascade. The main pharmacokinetic characteristics of rivaroxaban are a bioavailability of approximately 80-100%, a maximum concentration obtained in 2 to 4 hours, a terminal half-life of elimination of 7 to 11 hours, a renal elimination for 1/3 for the active hepatic metabolism from the cytochrome P450 (3A4) for the other 2/3. The main sources of variability are the renal and the liver function and potential interactions with some strong inhibitors or inducers of the CYP450 3A4. Phase II clinical studies have shown that this compound can be orally administrated, once or twice daily, without any biological monitoring and without any need for dose adjustment. There is a contra-indication in case of severe liver insufficiency and not recommended in case of severe renal impairment. Pharmacodynamically, Rivaroxaban is a direct and selective factor Xa inhibitor without any effect on the factor IIa and without any interaction on platelets. Four phases II with 2787 patients were carried out to for venous thromboembolic (VTE) prophylaxis after major orthopaedic surgery, showing that 10 mg once daily could be the optimal dose regimen to assess in phase III. Two phases II with 1446 patients were carried out for the treatment of VTE showing that 15 mg twice daily for 3 weeks and then 20 mg once daily could be the optimal dose regimen to evaluate in the following phases 3. No strong signal for a potential liver toxicity was shown during these 6 phases II.

Topics: Administration, Oral; Aged; Anticoagulants; Biological Availability; Clinical Trials as Topic; Contraindications; Cytochrome P-450 CYP3A; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Metabolic Clearance Rate; Middle Aged; Molecular Structure; Morpholines; Orthopedic Procedures; Postoperative Complications; Preanesthetic Medication; Rivaroxaban; Thiophenes; Venous Thrombosis

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

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

Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes.. This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365.. Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180.. Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time.. URL: https://www.. gov; Unique identifier: NCT03178864.

Topics: Adolescent; Adult; Anticoagulants; Canada; Feasibility Studies; Female; Headache; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Prospective Studies; Quality of Life; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic isolated distal deep vein thrombosis (IDDVT). In real-world clinical practice, both therapeutic and prophylactic anticoagulation are used for acute IDDVT. However, therapeutic anticoagulation is associated with higher risk of bleeding than prophylactic anticoagulation. Thus, this study aims to assess the efficacy and safety in patients with first acute symptomatic IDDVT treated with therapeutic or prophylactic anticoagulation using rivaroxaban.. This study is a prospective, multicentre, single-blind, randomised controlled trial. Outpatients with a first, acute, symptomatic, objectively confirmed IDDVT in four centres from 1 August 2021 are recruited. Eligible patients are randomised in a 1:1 ratio to receive prophylactic anticoagulation (rivaroxaban 10 mg once a day for 3 months) or therapeutic anticoagulation (rivaroxaban 20 mg once a day for 3 months). All patients are followed for 6 months. The primary efficacy outcome is radiographically confirmed recurrent venous thromboembolism. The primary safety outcome is the incidence of major or clinically relevant non-major bleeding events.. This study has been approved by the Ethics Committee of Zhongshan Hospital Fudan University (B2021-175R). Study results will be disseminated through peer-reviewed journals.. NCT04967573.

Topics: Anticoagulants; Hemorrhage; Humans; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Single-Blind Method; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.

Topics: Adult; Anticoagulants; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Rivaroxaban; Splanchnic Circulation; Venous Thrombosis

Warfarin and rivaroxaban were the two most commonly-used anticoagulant drugs for Deep venous thrombosis (DVT). The aim of this study was to explore the effects of post-discharge pharmacist-led follow-up on drug treatment in patients with DVT in primary hospitals from a pharmacological perspective. A total of 125 patients were recruited from July 2017 to June 2019 and randomized to either a control group or an intervention group. The control group was given routine medication guidance, clinical pharmacists followed up at 3 and 6 months after discharge. The intervention group was based on the control group and was followed up weekly for 6 months after discharge. For patients taking warfarin, the percentage of time in therapeutic range (TTR) and TTR>65% were significantly higher in the intervention group (p<0.05) and they also had less frequent dose changes. For patients taking warfarin or rivaroxaban, vascular ultrasonography showed better improvement rate in the intervention group (p<0.05). Pharmacist-led follow-up showed that the medication adherence (p<0.05) were significantly improved. There were lower risks of total and minor hemorrhage events and thrombosis events in the intervention group (p<0.05). Pharmacist-led follow-up not only reduced the risk of hemorrhage and thrombosis events, but also improved adherence to anticoagulation drugs.

Topics: Aftercare; Follow-Up Studies; Hemorrhage; Hospitals; Humans; Patient Discharge; Pharmacists; Rivaroxaban; Thrombosis; Venous Thrombosis; Warfarin

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

Topics: Administration, Oral; Antithrombins; Arthroplasty; Dabigatran; Humans; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thrombosis

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

To assess the efficacy and safety of long-term diosmin 600 therapy added to rivaroxaban and elastic compression stockings (ECS) in patients with femoropopliteal deep vein thrombosis (DVT).. This single-center, open-label randomized clinical trial RIDILOTT DVT enrolled patients with their first femoropopliteal DVT confirmed by duplex ultrasound scan (DUS). Participants were randomly allocated to the control group (standard treatment with rivaroxaban for six months and ECS for 12 months) or the experimental group (standard treatment with the additional use of diosmin 600 mg once daily for 12 months). Patients were followed for 12 months. The primary outcome was post-thrombotic syndrome (PTS), according to the Villalta Score (≥5). The secondary outcomes were deep vein recanalization, chronic venous disease (CVD) progression, the severity of PTS (Villalta), and CVD (VCSS), quality of life (CIVIQ-20), venous thromboembolism recurrence, and adverse event (AE).. Ninety patients were randomized (45 per group). There were 56 men and 34 women with a mean age of 57.8±13.4 years, and 69% had clinically unprovoked DVT. PTS frequency at 12 months was significantly lower (8.9% vs. 48.9%) in the experimental group compared with control one (relative risk, 0.14; 95% confidential interval, 0.04-0.43, P<0.001). Adding diosmin 600 was associated with quicker and complete vein recanalization, lower CVD progression rate, and lower Villalta, VCSS, and CIVIQ-20 scores. There was no difference in recurrent DVT or AE.. Adjunctive use of diosmin 600 to rivaroxaban and ECS in patients with femoropopliteal DVT can improve the clinical and ultrasound outcomes after 12 months of treatment.

Topics: Adult; Aged; Diosmin; Female; Humans; Male; Middle Aged; Postthrombotic Syndrome; Quality of Life; Rivaroxaban; Treatment Outcome; Venous Thrombosis

Rivaroxaban, a novel oral anticoagulant drug, is widely used in clinical practice. There is no standardized laboratory monitoring for rivaroxaban, and its plasma concentration in Chinese patients with deep vein thrombosis is unclear. The rivaroxaban concentrations in human plasma and determine the steady-state concentration of rivaroxaban in patients with deep vein thrombosis are needed.. An ultra-high-performance liquid chromatography with mass spectrometric detection method was developed. Chromatographic separation was performed on a Waters BEH C18 column with isocratic elution using a mobile phase composed of acetonitrile and water. Quantitation of the analytes was performed using positive ionization mode and mass transitions of m/z 437.3 → m/z 145.0 and m/z 440.1 → m/z 145.0 for rivaroxaban and the internal standard, respectively. Blood samples were collected at 0 h and 2 h after patients took rivaroxaban for 7 days or more.. The method was validated over the concentration range of 0.5 ~ 400 ng•mL. The plasma rivaroxaban concentration in patients who took 10 mg rivaroxaban twice daily fluctuated less than that in patients who took 20 mg rivaroxaban once daily. The plasma concentration can be used for therapeutic drug monitoring for rivaroxaban.

Topics: Adult; Aged; Asian People; Blood Coagulation Tests; Chromatography, High Pressure Liquid; Drug Monitoring; Factor Xa Inhibitors; Humans; Middle Aged; Rivaroxaban; Tandem Mass Spectrometry; 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

Balloon dilatation with stent implantation has been proved to be an effective option for left iliac vein compression syndrome (LIVCS), but thrombosis may still occur after the operation. Currently, warfarin is used for anticoagulant therapy, but long-term monitoring is required, while rivaroxaban does not need laboratory monitoring, which can simplify treatment. Therefore, this study aimed to compare the efficacy and safety of rivaroxaban and warfarin in anticoagulation.. This study is a multicenter, randomized controlled trial. We will recruit 224 patients with thrombotic LIVCS from 9 hospitals. Moreover, these patients will be randomized to either the experimental group (rivaroxaban) or the control group (warfarin plus nadroparin). The primary outcome is stent occlusion rate. Secondary outcomes are quality of life scale survey results, all-cause mortality, anticoagulation-related mortality, and the proportion of participants with stent displacement/fracture, thrombosis, hemorrhage, and other vascular events.. This study will provide reliable, evidence-based clinical evidence for the efficacy and safety of rivaroxaban antithrombotic therapy after stent implantation.. ClinicalTrials.gov NCT04067505 . Registered on August 26, 2019.

Topics: Anticoagulants; Humans; Iliac Vein; Multicenter Studies as Topic; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Rivaroxaban; Stents; Treatment Outcome; Venous Thrombosis

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist). The main treatment period was 3 months. The primary efficacy outcome, symptomatic recurrent venous thromboembolism (VTE), and principal safety outcome, major or clinically relevant nonmajor bleeding,were centrally evaluated by blinded investigators. Sinus recanalization on repeat brain imaging was a secondary outcome. Statistical analyses were exploratory. In total, 114 children with confirmed CVT were randomized. All children completed the follow-up. None of the 73 rivaroxaban recipients and 1 (2.4%; CVT) of the 41 standard anticoagulant recipients had symptomatic, recurrent VTE after 3 months (absolute difference, 2.4%; 95% confidence interval [CI], -2.6% to 13.5%). Clinically relevant bleeding occurred in 5 (6.8%; all nonmajor and noncerebral) rivaroxaban recipients and in 1 (2.5%; major [subdural] bleeding) standard anticoagulant recipient (absolute difference, 4.4%; 95% CI, -6.7% to 13.4%). Complete or partial sinus recanalization occurred in 18 (25%) and 39 (53%) rivaroxaban recipients and in 6 (15%) and 24 (59%) standard anticoagulant recipients, respectively. In summary, in this substudy of a randomized trial with a limited sample size, children with CVT treated with rivaroxaban or standard anticoagulation had a low risk of recurrent VTE and clinically relevant bleeding. This trial was registered at clinicaltrials.gov as #NCT02234843.

Topics: Anticoagulants; Child; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

To evaluate the efficacy of oral rivaroxaban compared to warfarin in patients with deep vein thrombosis (DVT).. Open label randomized controlled study.. Department of General Medicine, Pakistan Institute of Medical Sciences (PIMS), Islamabad from January 2016 to January 2018.. Patients of both genders between 18 and 60 years of age with Doppler ultrasound-confirmed DVT were included in the study. Pregnant patients and those with advanced liver, renal disease, those with a previous history of DVT, malignancy, with a platelets count of less than 50000/ul were excluded from the study. Rivaroxaban was given in a dose of 15 mg twice daily for 21 days followed by 20 mg once daily. Patients in the warfarin group were given heparin for 3 to 5 days followed by warfarin for 3 to 6 months. The primary efficacy outcome was patency of the vessel at 3 and 6 months of treatment. The principal safety outcomes were major and minor bleeding during the study period.. A total of 151 patients with acute symptomatic deep vein thrombosis were enrolled in the study. Half of the patients were given warfarin and the other half rivaroxaban for 6 months. At three months, there were no significant differences observed in vessel patency in the rivaroxaban group (22.4%) as compared to warfarin group (26.7%) but after 6 months of therapy, vessel patency was significantly more in the rivaroxaban group. Adverse events did not show any significant differences Conclusion: Rivaroxaban had an efficacy superior to warfarin in terms of vessel patency after six months of therapy but adverse events were similar in both the groups.

Topics: Administration, Oral; Adult; Drug Administration Schedule; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pakistan; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Young Adult

Recently non-Vitamin K antagonist oral anticoagulants (NOAC) is replacing warfarin for the treatment of deep vein thrombosis (DVT). However, the role of NOAC after thrombolysis of acute iliofeomral DVT (IFDVT) is not yet defined. This randomized clinical trial aimed to compare the safety and efficacy of rivaroxaban versus warfarin after catheter directed thrombolysis of an IFDVT. Patients with acute DVT of both the iliac and the femoral vein (n = 72) were recruited and randomized to either standard anticoagulation (enoxaparin and warfarin, n = 35) or rivaroxaban (n = 37) after successful thrombolysis or mechanical thrombectomy. Primary efficacy outcome was a recurrence of any venous thromboembolism (VTE) within 6 months. Secondary safety outcomes included major bleeding, clinically relevant non-major bleeding (CRNMB), other adverse event, and all-cause mortality. Rate of recurrent VTE were similar in both groups (11.4% versus 12.5%; p = 0.94). Major bleeding or CRNMB was less in rivaroxaban group without significance (2.9% versus 9.4%, HR, 0.31; 95% CI, 0.03-2.96; p = 0.31). Recurrence-free survival and major bleeding-free survival at 6 months were not different in both groups. After thrombolysis of acute IFDVT, rivaroxaban was as safe and effective as warfarin in preventing DVT recurrence.

Topics: Aged; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Retreatment; Risk Factors; Rivaroxaban; Thrombolytic Therapy; Treatment Outcome; Venous Thrombosis

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

Anticoagulation therapy is the main line of treatment for acute portal vein thrombosis (PVT) in the absence of cirrhosis. However, the use of this therapy in cirrhotic PVT is still with doubtful evidence. We aimed to evaluate the efficacy and safety of rivaroxaban compared to warfarin for the management of acute non-neoplastic PVT in Hepatitis C virus (HCV)-related compensated cirrhosis.. Out of 578 patients with chronic HCV infection, 80 patients with acute PVT who had undergone splenectomy due to hypersplenism and 4 patients with acute PVT due to portal pyemia were selected. The patients were randomly assigned (1:1) to the study group (n = 40), in which the patients received rivaroxaban 10 mg/12 h, or the control group (n = 40), in which the patients received warfarin.. In the rivaroxaban group, the resolution of PVT was achieved in 34 patients (85%) within 2.6 ± 0.4 months and delayed, partial recanalization after 6.7 ± 1.2 months (n = 6.15%). Complications such as major bleeding, abnormal liver functions, death, or recurrence did not occur during treatment, and patients in this group showed improved short-term survival rate (20.4 ± 2.2 months) compared to the survival rate in the control group (10.6 ± 1.8 months) in which warfarin achieved complete resolution in 45% of patients. Complications such as severe upper GI tract bleeding (43.3%), hepatic decompensation (22.5%), progression to mesenteric ischemia (12.5%), recurrence (10%), and death (20%) were observed in the control group. The duration until complete resolution of thrombus correlated with age, the extent of the thrombus, creatinine level, and MELD score. The recurrence after complete resolution of thrombus correlated with age, the extent of the thrombus, thrombogenic gene polymorphism, and the use of warfarin.. Rivaroxaban was effective and safe in acute HCV-related non-neoplastic PVT with improved short-term survival rate; ClinicalTrials.gov Identifier: NCT03201367.

Topics: Adult; Anticoagulants; Blood Coagulation; Computed Tomography Angiography; Egypt; Factor Xa Inhibitors; Female; Hemorrhage; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Phlebography; Portal Vein; Recurrence; Rivaroxaban; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis; Warfarin

Cancer patients have a four- to fivefold greater risk of thrombosis than the general population. Recommended treatment for cancer-associated thrombosis is 3-6 months of low-molecular-weight heparin. The 'select-d' trial is an open-label, randomised, multi-centre pilot trial in patients with cancer-associated thrombosis, utilising dalteparin (low-molecular-weight heparin) versus rivaroxaban (a direct oral anticoagulant), to assess effectiveness and safety.. To explore patient and informal carers' experiences of cancer-associated thrombosis and their experience and understanding of the risk-benefit of thrombosis treatment.. Qualitative substudy of the select-d trial, using semi-structured interviews. Interviews were audio-recorded and transcribed. Data were analysed using Framework Analysis.. Participants were purposively sampled ( n = 37 patients; 46% male; age 40-89; 9 with carer present).. Three themes were found: experience of cancer-associated thrombosis, experience of anticoagulation and risk-benefit balance of the two modes of administration. Some were shocked by their thrombosis diagnosis (most were unaware of their risk), but others found it insignificant compared with cancer. Most patients found tablets more convenient, but injections were acceptable in the context of having cancer. While most were happy to follow medical advice, others weighed preference on the basis of effectiveness.. Lack of awareness of thrombosis risk is concerning; cancer patients must be informed to enable prompt help-seeking. Tablets could provide a welcome choice for patients if there is equivalent risk-benefit to injected anticoagulants. Patients trust their clinicians to tailor their treatment. Future research could explore the effect of routine information giving about the risk of thrombosis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Factor Xa Inhibitors; Female; Humans; Injections; Male; Middle Aged; Neoplasms; Patient Satisfaction; Rivaroxaban; Venous Thrombosis

The aim of this study was to assess the impact of adding long-term micronized purified flavonoid fraction (MPFF) to standard treatment of femoropopliteal deep vein thrombosis (DVT).. This pilot, comparative, open-label study with blinded outcome assessor enrolled patients with a first episode of femoropopliteal DVT confirmed by duplex ultrasound scanning (DUS). All participants were randomly allocated to one of two treatment groups: (1) control that received a standard treatment with oral rivaroxaban, and (2) experimental that involved additional treatment with MPFF 1000 mg/day. Both drugs were used for 6 months. Patients were followed for the whole treatment period and underwent DUS every 2 months to determine the degree of recanalization by popliteal (PV), femoral vein (FV), and common femoral vein (CFV) compressibility. Thrombi extension were assessed by the modified Marder score. At the end of the follow-up period, patients were assessed with Villalta and venous clinical severity scales (VCSS). Patients with a Villalta score ≥ 5 were diagnosed with post-thrombotic syndrome (PTS).. Sixty patients were randomized to the control or MPFF groups (n = 30 in each group). There were 40 men and 20 women with a mean age ± SD of 56.3 ± 13.4 years. Clinically unprovoked DVT was recognized in 65% of cases and left side localization in 45%. The mean baseline Marder score was 15.0 ± 4.8 and 11.1 ± 4.3 in the experimental and control groups, respectively (p = 0.002). At 6 months, the mean Villalta score in the MPFF group was significantly lower compared with control (2.9 ± 2.7 versus 5.8 ± 3.0; p < 0.0001). PTS was diagnosed in six patients (20%) and 17 patients (57%) in the experimental and control groups respectively (p = 0.007). A significant difference between the groups was also observed for the VCSS value (2.3 ± 1.9 versus 4.9 ± 1.9; p < 0001). After 6 months of treatment the Marder score decreased to 0.8 ± 1.6 and 2.8 ± 3.5 in the experimental and control groups, respectively (p = 0.006). In the MPFF group, there was a greater reduction in the Marder score (p < 0.0001) and more rapid rate of recanalization for the FV (p < 0.0001), with a non-significant trend for the CFV (p = 0.130) and PV (p = 0.204) compared with the control group. Full recanalization of the PV at 6 months was observed in 24 patients (80%) who had received MPFF, and only 17 patients (57%) in the control group (p = 0.095).. The addition of MPFF to standard therapy for DVT in the form of oral rivaroxaban can reduce the incidence of PTS at 6 months in patients with proximal DVT and increase the speed of deep vein recanalization.. Les Laboratoires Servier funded the article processing fees, editorial assistance, and open access fee for this manuscript.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Flavonoids; Humans; Male; Middle Aged; Postthrombotic Syndrome; Rivaroxaban; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Thrombosis

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

In this article, we report the outcomes of patients with deep venous thrombosis in the lower limbs treated with the oral anticoagulant rivaroxaban or warfarin, focusing on the recanalization rate (measured with duplex ultrasound) and the incidence of postthrombotic syndrome.. This was a prospective, consecutive, randomized, blind cohort study of patients admitted with deep venous thrombosis to the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between March 2016 and July 2018. The patients were randomized into 2 groups and treated with oral anticoagulation for 6 months: either rivaroxaban (group 1) or warfarin (group 2). The study was registered at clinicaltrials.gov under NCT 02704598.. Eighty-eight patients with deep venous thrombosis were admitted to the Vascular Surgery Department and randomized into the 2 groups. The follow-up time was 360 days. Analyses were performed at 180 and 360 days. Four patients were excluded from the study during follow-up because of a diagnosis of ovarian cancer (1 patient), head and neck cancer (1 patient), lung cancer (1 patient), and stomach cancer (1 patient). Therefore, 84 patients were evaluated: 46 patients in group 1 and 38 in group 2. The incidence of postthrombotic syndrome was 17.9% (15 cases) in the total cohort, but was significantly higher in group 2 (11 cases, 28.9%) than in group 1 (4 cases, 8.7%; P < .001; odds ratio, 4.278). The rate of total venous recanalization at 360 days was 40.5% (34 patients) in the total cohort, but was significantly higher in group 1 (35 patients, 76.1%) than in group 2 (5 patients, 13.2%; P < .001). The incidence of partial venous recanalization was 46.4% and was significantly higher in group 2 (28 patients, 73.7%) than in group 1 (11 patients, 23.9%; P = .016). Five patients in the total cohort (6%) showed no venous recanalization, all of them in group 2 (P = .016).. In this study, patients who received oral rivaroxaban displayed a lower incidence of postthrombotic syndrome and a better total vein recanalization rate after 6 and 12 months than patients who received warfarin.

Topics: Administration, Oral; Anticoagulants; Brazil; Female; Follow-Up Studies; Humans; Incidence; Lower Extremity; Male; Middle Aged; Postthrombotic Syndrome; Prospective Studies; Rivaroxaban; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency; Venous Thrombosis; Warfarin

Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy.. In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding.. Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23).. Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .).

Topics: Aftercare; Aged; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Discharge; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The optimal anticoagulant following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) is unknown.. From the Swiss Venous Stent registry, an ongoing prospective cohort study, we performed a subgroup analysis of patients with acute IFDVT who underwent catheter-based early thrombus removal followed by nitinol stent placement. Duplex ultrasound and Villalta scores were used to determine patency rates and incidence of the post-thrombotic syndrome (PTS) in patients treated with either rivaroxaban (n = 73) or a vitamin K-antagonist (VKA; n = 38) for a minimum duration of 3 months.. Mean follow-up duration was 24 ± 19 months (range 3 to 77 months). Anticoagulation therapy was time-limited (3 to 12 months) in 56% of patients (47% in the rivaroxaban group and 58% in the VKA group, p = 0.26), with shorter mean duration of anticoagulation in the rivaroxaban group (180 ± 98 days versus 284 ± 199 days, p = 0.01). Overall, primary and secondary patency rates at 24 months were 82% (95%CI, 71-89%) and 95% (95%CI, 87-98%), respectively, with no difference between the rivaroxaban (87% [95%CI, 76-94%] and 95% [95%CI, 85-98%]) and the VKA group (72% [95%CI, 52-86%] and 94% [95%CI, 78-99%]; p > 0.10 for both). Overall, 86 (86%) patients were free from PTS at latest follow-up, with no difference between the rivaroxaban and the VKA groups (57 [85%] versus 29 [88%]; p = 0.76). Two major bleeding complications (1 in each group) occurred in the peri-interventional period, without any major bleeding thereafter.. In patients with acute IFDVT treated with catheter-based early thrombus removal and venous stent placement, the effectiveness and safety of rivaroxaban and VKA appear to be similar.. The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

Topics: Adult; Aged; Anticoagulants; Catheterization; Endovascular Procedures; Factor Xa Inhibitors; Female; Femoral Vein; Humans; Iliac Vein; Male; Middle Aged; Postthrombotic Syndrome; Prospective Studies; Rivaroxaban; Stents; Thrombolytic Therapy; Treatment Outcome; Vascular Patency; Venous Thrombosis; Vitamin K

XALIA assessed the safety and effectiveness of rivaroxaban for deep vein thrombosis (DVT) treatment in routine clinical practice. This substudy describes the clinical characteristics and outcomes of 'early switchers' - patients who received heparin or fondaparinux for >2-14days and/or a vitamin K antagonist (VKA) for 1-14days before switching to rivaroxaban.. Patients with DVT (latterly with concomitant pulmonary embolism) received rivaroxaban or standard anticoagulation (initial treatment with heparin or fondaparinux, usually overlapping with and followed by a VKA). Patients administered rivaroxaban alone, or heparin or fondaparinux for ≤48h pre-enrollment were included in the rivaroxaban cohort. Therapy type, dose, and duration were at the physician's discretion. Primary outcomes were major bleeding, recurrent venous thromboembolism (VTE), and all-cause mortality.. In 368 early switchers, recurrence or bleeding risk factors were more prevalent versus the rivaroxaban cohort, including creatinine clearance<50mL/min (6.5% vs. 3.9%), previous major bleeding (4.6% vs. 1.4%), active cancer (8.2% vs. 5.6%), and concomitant pulmonary embolism (20.9% vs. 8.4%). Crude incidence rates were numerically higher versus the rivaroxaban cohort for major bleeding (1.4% vs. 0.7%), recurrent VTE (2.2% vs. 1.4%), and all-cause mortality (0.8% vs. 0.5%).. Patients who switched to rivaroxaban early in the treatment process had a higher frequency of risk factors for bleeding and recurrent VTE than patients treated with rivaroxaban; reflected by the higher risk of adverse events in that group during follow-up.

Topics: Adult; Aged; Anticoagulants; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Rivaroxaban; Treatment Outcome; Venous Thrombosis

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

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

Patients with superficial vein thrombosis (SVT) are commonly treated with low-molecular weight heparin or fondaparinux in prophylactic, intermediate or therapeutic dosages for treatment periods of 10-45 days. This practice is also reflected by the current guideline recommendations. However, given the broad range of thromboembolic complication rates in SVT (between 0 and 30 % have been reported) it seems reasonable to suspect that risk stratification is needed to differentiate patients at low risk who may not benefit from anticoagulation from those at high risk who may need higher dosages or a longer duration of anticoagulation. Furthermore, prolonged treatment with injectable anticoagulants has been shown to result in poor patient adherence. Direct oral anticoagulants have recently been approved for venous thromboembolism therapy and these new drugs may offer advantages also for SVT patients. The prospective, randomized, open-label, blinded adjudication trial superficial phlebitis treated for 45 days with rivaroxaban versus fondaparinux (SURPRISE) will evaluate the efficacy and safety of 10 mg rivaroxaban OD compared to fondaparinux 2.5 mg OD for SVT treatment in a subset of high-risk SVT patients over a treatment period of 45 days. The purpose of the study is to demonstrate non-inferiority of rivaroxaban compared to fondaparinux in preventing the combined efficacy endpoint of thrombus progression, SVT recurrence, DVT, PE and death. The results of the SURPRISE trial will provide evidence for the concept of risk stratification in SVT and for the value of rivaroxaban 10 mg in SVT treatment (clinicaltrials.gov NCT01499953).

Topics: Disease Progression; Fondaparinux; Humans; Polysaccharides; Recurrence; Risk Assessment; Rivaroxaban; Single-Blind Method; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8 % vs 6.1 %, respectively, p=0.03; absolute risk difference, -5.3 %, 95 % CI, -11.4 to -0.8; crude relative risk 0.14, 95 % CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected "high-risk" subjects, remains to be determined. A larger trial to verify our preliminary results is warranted.

Topics: Adult; Anterior Cruciate Ligament Reconstruction; Arthroscopy; Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Knee Joint; Male; Meniscectomy; Middle Aged; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

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

We conducted a prospective, single-center, active controlled study from July 2013 to January 2015, in Chinese patients with rapid ventricular arrhythmia who had received radiofrequency catheter ablation (RFCA) treatment to determine formation of lower extremity deep vein thrombosis (LDVT) post RFCA procedure, and evaluated the effect of rivaroxaban on LDVT. Patients with asymptomatic pulmonary thromboembolism who had not received any other anticoagulant and had received no more than 36 hours of treatment with unfractionated heparin were included. Post RFCA procedure, patients received either rivaroxaban (10 mg/d for 14 days beginning 2-3 hours post-operation; n = 86) or aspirin (100 mg/d for 3 months beginning 2-3 hours post-operation; n = 90). The primary outcome was a composite of LDVT occurrence, change in diameter of femoral veins, and safety outcomes that were analyzed based on major or minor bleeding events. In addition, blood flow velocity was determined. No complete occlusive thrombus or bleeding events were reported with either of the group. The lower incidence rate of non-occluded thrombus in rivaroxaban (5.8%) compared to the aspirin group (16.7%) indicates rivaroxaban may be administered post-RFCA to prevent and treat femoral venous thrombosis in a secure and effective way with a faster inset of action than standard aspirin therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Aspirin; Catheter Ablation; China; Female; Femoral Vein; Humans; Lower Extremity; Male; Middle Aged; Prospective Studies; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Young Adult

The aims of this study were to investigate the effects of rivaroxaban on routine coagulation assays using our local, widely available, reagents and to study the relationship between sensitive coagulation assays and bleeding risk caused by rivaroxaban.. Prothrombin time (PT), activated partial thromboplastin time (APTT) and anti-factor Xa (FXa) chromogenic assays (Biophen DiXaI) and inhibition of FXa activity were performed in normal pooled plasma (NPP) spiked with rivaroxaban and plasma samples from patients treated with rivaroxaban.. In vitro, the linear correlation coefficient of measured concentrations of rivaroxaban, by Biophen DiXaI, and spiked concentrations of rivaroxaban was 0.99. PT and APTT showed good linear correlation with rivaroxaban concentrations, while other assays showed poor correlation. In vivo, PT showed a moderate linear correlation with rivaroxaban concentrations while APTT had a weak correlation with rivaroxaban concentrations. In vitro and in vivo, the rivaroxaban concentrations, measured by Biophen DiXaI, always showed good correlation with the inhibition of FXa activity, and PT values showed moderate correlation with the inhibition of FXa activity.. Biophen DiXaI can be considered as a quantitative method to monitor the anticoagulation activity of rivaroxaban, and could be used to evaluate bleeding risk caused by rivaroxaban. The PT reagent (Thrombosis S) could be considered as a rough method to monitor the anticoagulation activity of rivaroxaban and evaluate bleeding risk caused by rivaroxaban.

Topics: Adult; Aged; Blood Coagulation; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Rivaroxaban; Venous Thrombosis; Young Adult

Post-thrombotic syndrome (PTS) is a common complication of deep-vein thrombosis (DVT). Poor quality treatment with vitamin K antagonists (VKA) is a risk factor for PTS. We hypothesised that treatment with the direct oral anticoagulant (DOAC) rivaroxaban may lower PTS incidence as compared to enoxaparin/VKA, as DOACs have a more stable pharmacologic profile than VKA. We performed a post-hoc subgroup analysis of the Einstein DVT trial (n=3449). Kaplan-Meier survival analysis was performed to compare the cumulative incidence of PTS between the rivaroxaban and enoxaparin/VKA groups. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models. We included 336 patients with a mean age of 58 ± 16 years and a median follow-up after index DVT of 57 months (interquartile range 48-64). Of these, 162 (48 %) had been treated with rivaroxaban and 174 (52 %) with enoxaparin/VKA. The cumulative PTS incidence at 60 months follow-up was 29 % in the rivaroxaban group and 40 % in the enoxaparin/VKA group. After adjusting for age, gender, body mass index, previous VTE, ipsilateral recurrent DVT, extent of DVT, idiopathic DVT, duration of anticoagulant treatment, compliance to assigned study medication, elastic compression stocking use and active malignancy, the HR of PTS development for rivaroxaban was 0.76 (95 % CI: 0.51-1.13). In conclusion, treatment of acute DVT with rivaroxaban was associated with a numerically lower but statistically non-significant risk of PTS compared to enoxaparin/VKA treatment. The potential effect on reducing PTS deserves evaluation in a large randomised trial.

Topics: Adult; Aged; Anticoagulants; Enoxaparin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postthrombotic Syndrome; Recurrence; Rivaroxaban; Survival Analysis; Treatment Outcome; Venous Thrombosis; Vitamin K

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

Prevention of deep venous thrombosis (DVT) and associated pulmonary embolism following major orthopedic surgeries is challenging, and there is an increased interest in developing new treatment strategies. We compared 2 switch-therapy modalities-enoxaparin to rivaroxaban and enoxaparin to dabigatran-and enoxaparin monotherapy for preventing DVT after total knee arthroplasty (TKA) and total hip arthroplasty (THA).. This was a prospective, non-blinded, randomized controlled study. We selected 180 eligible patients out of 247 patients undergoing TKA or THA. During the preoperative checkup, patients were randomized to receive either enoxaparin (enoxaparin group) or switch-therapy regimens, comprising enoxaparin during hospitalization and rivaroxaban (rivaroxaban group) or dabigatran (dabigatran group) during the outpatient period. All patients were evaluated for DVT using Doppler ultrasonography (USG) 6 weeks postoperatively. The primary efficacy outcome was the prevention of symptomatic or Doppler ultrasonography (USG)-proven DVT, whereas the primary safety outcome was the incidence of bleeding during the DVT-prophylaxis period.. Doppler USG at 6 weeks after surgery revealed no signs of DVT in any patient. During the hospitalization period, only 2 major bleeding events were reported (1 [1.6%] in the enoxaparin group and 1 [1.6%] in the dabigatran group). No major bleeding events were reported during the outpatient follow-up period in any group. Differences among the 3 groups regarding bleeding events were not statistically significant (p>0.05).. When using switch-therapy modalities, clinicians can take advantage of the safety of enoxaparin during the hospitalization period and ease of use of new oral anticoagulant drugs during the outpatient period.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dabigatran; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Rivaroxaban; Ultrasonography, Doppler; Venous Thrombosis

This is a retrospective cohort study of adults with a primary diagnosis of deep venous thrombosis (DVT) unaccompanied by pulmonary embolism (PE), seen in 4 emergency departments in 2013 and part of 2014. The purpose was to assess the prevalence of home treatment of DVT in the present era of new oral anticoagulants. Among 96 patients with DVT and no PE, 85 (88.5%) were hospitalized and 11 (11.5%) were discharged to home. Most of the patients discharged to home received low-molecular-weight heparin, 9 (81.8%) of 11. None were prescribed new oral anticoagulants. Early discharge in ≤2 days occurred 28 (32.9%) of 85 patients. Most (64.3%) received enoxaparin and/or warfarin at early discharge. Rivaroxaban was prescribed in 7 (25.0%) of those discharged in ≤2 days. We conclude that in some emergency departments, patients with DVT are uncommonly discharged to home even though new oral anticoagulants are available.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Enoxaparin; Female; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

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 study the effect of autologous drained blood reinfusion on hidden blood loss and limb swelling following rivaroxaban anticoagulation for primary total hip arthroplasty.. From May, 2011 to October, 2012, 98 patients undergoing primary unilateral total hip arthroplasty received rivaroxaban therapy for prevention of deep venous thrombosis (DVT). Forty-five of the patients used a drained blood reinfusion device (group A) and 53 patients did not (group B). Hidden blood loss and the maximal changes of postoperative circumferential length of the mid-thigh were measured and compared between the two groups.. The mean total blood loss, the hidden blood loss, and the maximal changes of postoperative thigh circumference were 1591.1∓337.3 ml, 1591.1∓337.3 ml, and 5.1∓2.8 cm in group A, as compared to 1374.5∓317.3 ml, 467∓96.8 ml, 3.9∓1.4 cm in group B, respectively. The two groups showed a significant difference in the maximal changes of postoperative mid-thigh circumference (P<0.01) but not in hidden blood loss (P>0.05).. Reinfusion of autologous drained blood does not affect hidden blood loss but can increase limb swelling following primary total hip arthroplasty with rivaroxaban anticoagulation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Blood Transfusion, Autologous; Edema; Female; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

This study aimed to compare the efficacy and safety of aspirin, rivaroxaban and low-molecular-weight heparin (LMWH) for post total knee arthroplasty (TKA) deep vein thrombosis (DVT) prophylaxis. Between July 2011 and July 2013, a prospective randomized controlled trial was performed on 324 patients with osteoarthritis who underwent primary unilateral TKA. Twelve hours after the surgery, Group A was given oral rivaroxaban at a dose of 10 mg/day. Group B was given subcutaneous LMWH at a dose of 4000 AxaIU (0.4 ml)/day and Group C was given oral aspirin at a dose of 100 mg/day. All three groups were treated for 14 days, and all of the patients were followed for 4 weeks. The incidence of DVT, dominant/hidden blood loss, the incidence of wound complications and the incidence of subcutaneous ecchymosis in the affected extremities were compared between the three groups. The incidence of DVT was lower in Group A compared with the other two groups [3 (2.94%) vs. 14 (12.50%), P = 0.029; 3 (2.94%) vs. 18 (16.36%), P = 0.017]. However, hidden blood loss [1.71 (1.19-2.97) vs. 1.18 (0.77-2.31), P = 0.009; 1.71 (1.19-2.97) vs. 1.30 (0.61-2.43), P = 0.004] and wound complications [5 (4.90) vs. 3 (2.67), P = 0.027; 5 (4.90) vs. 2 (1.82), P = 0.014] were more common in Group A than in the other groups. There were no significant differences between Group B and Group C in the incidence of DVT [14 (12.50%) vs. 18 (16.36%), P = 0.831], hidden blood loss [1.18 (0.77-2.31) vs. 1.30 (0.61-2.43), P = 0.327] or wound complications [3 (2.67) vs. 2 (1.82), P = 0.209]. No significant differences in the incidence of limb swelling were found between the three groups [38 (37.25%) vs. 28 (25.00%) vs. 24 (21.82%), P = 0.247]. Group A had a higher incidence of subcutaneous ecchymosis in the affected extremities than Group C [74 (72.55%) vs. 54 (49.09%), P = 0.039], but there were no significant differences between Groups A and B [74 (72.55%) vs. 62 (55.36%), P = 0.193] or between Groups B and C [62 (55.36%) vs. 54 (49.09%), P = 0.427]. Rivaroxaban has a positive anticoagulation effect but leads to increases in both postoperative blood loss and wound complications in patients. Hence, clinicians using rivaroxaban for anticoagulant therapy should closely monitor the changes in the hemoglobin level and wound healing and promptly supplement blood volume and provide other symptomatic and supportive treatments. No significant difference in post-TKA DVT prophylaxis was found between aspirin and LMW

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Aspirin; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Morpholines; Prospective Studies; Rivaroxaban; Thiophenes; Venous Thrombosis

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

TB-402 is a long-acting monoclonal antibody that partially inhibits factor VIII. A single administration of TB-402 was effective and well-tolerated for the prevention of venous thromboembolism (VTE) after total knee replacement. In this study, the efficacy and safety of a single administration of TB-402 for the extended prophylaxis of VTE after total hip replacement (THR) was investigated. This was a phase II, randomised, active-controlled, double-blind study that included patients undergoing elective THR surgery. Patients were randomised to TB-402 25 mg or TB-402 50 mg, administered as a single intravenous administration 2-4 hours postoperatively, or to rivaroxaban 10 mg once daily for 35 days. The primary efficacy outcome was total VTE defined as symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) detected by bilateral venography at day 35. The principal safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding until day 35. Total VTE was similar in all groups: 5.3% (95%CI 2.9-9.6), 5.2% (95%CI 2.8-9.3) and 4.7% (95%CI 2.5-8.7) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. All were asymptomatic DVTs. Major or clinically relevant non-major bleedings were observed in 5.8% (95%CI 3.3-9.9), 7.2% (95%CI 4.4-11.6) and 1.4% (95%CI 0.5-4.2) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. In conclusion, TB-402, administered as a single postoperative dose, had a similar efficacy compared to rivaroxaban for the prevention of VTE after THR. The incidence of major and clinically relevant non-major bleeding was higher in the TB-402 groups than in the rivaroxaban group.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Patient Safety; Postoperative Complications; Risk; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Rivaroxaban, an oral, direct factor Xa inhibitor, has been approved for the treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and PE as a fixed-dose, single-drug regimen that does not require initial heparinisation, routine coagulation monitoring or dose adjustment. This study evaluated patient-reported treatment satisfaction in EINSTEIN DVT--a large, open-label, randomised study that compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy in patients with acute symptomatic DVT without PE. As part of EINSTEIN DVT, a total of 1,472 patients in seven countries were asked to complete a new, validated measure of treatment satisfaction--the Anti-Clot Treatment Scale (ACTS)--at scheduled visits throughout 12 months of treatment. ACTS scores were compared between study groups in the intention-to-treat population. Patients reported greater satisfaction in the rivaroxaban group compared with the enoxaparin/VKA group, with higher mean ACTS scores across visits. Mean ACTS Burdens scores were 55.2 vs 52.6 (p<0.0001) in favour of rivaroxaban, equivalent to a moderate effect size of 0.42. The treatment effect was consistent over time, with the mean score difference ranging from 2.18 (month 2) to 3.18 (month 12). Overall mean ACTS Benefits scores were 11.7 vs 11.5 in favour of rivaroxaban (p=0.006). This was associated with a small overall effect size of 0.12. The improvement in ACTS Benefits for rivaroxaban became apparent at month 2 and subsequent visits. Rivaroxaban results in improved treatment satisfaction compared with enoxaparin/VKA among patients with DVT, particularly in reducing patient-reported anticoagulation burden.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Patient Satisfaction; Rivaroxaban; Thiophenes; Venous Thrombosis

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

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Body Weight; Computer Simulation; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Models, Biological; Morpholines; Rivaroxaban; Stroke; Thiophenes; Venous Thrombosis; Young Adult

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

Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty; oral regimens could enable shorter hospital stays. We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty.. In a randomised, double-blind, phase III study, 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily, beginning 6-8 h after surgery, or subcutaneous enoxaparin 30 mg every 12 h, starting 12-24 h after surgery. Patients had mandatory bilateral venography between days 11 and 15. The primary efficacy outcome was the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or death from any cause up to day 17 after surgery. Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per-protocol population (absolute non-inferiority limit -4%); if non-inferiority was shown, we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population. The primary safety outcome was major bleeding. This trial is registered with ClinicalTrials.gov, number NCT00362232.. The primary efficacy outcome occurred in 67 (6.9%) of 965 patients given rivaroxaban and in 97 (10.1%) of 959 given enoxaparin (absolute risk reduction 3.19%, 95% CI 0.71-5.67; p=0.0118). Ten (0.7%) of 1526 patients given rivaroxaban and four (0.3%) of 1508 given enoxaparin had major bleeding (p=0.1096).. Oral rivaroxaban 10 mg once daily for 10-14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty.. Bayer Schering Pharma AG, Johnson & Johnson Pharmaceutical Research & Development.

Topics: Administration, Oral; Aged; Analysis of Variance; Anticoagulants; Arthroplasty, Replacement, Knee; Double-Blind Method; Enoxaparin; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Morpholines; Phlebography; Risk Reduction Behavior; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Treatment Outcome; Venous Thrombosis

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

We performed a randomized dose-ranging study, double-blind for rivaroxaban doses and open-label for the comparator (low-molecular-weight heparin followed by vitamin K antagonists) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator. Treatment lasted for 84 days. The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline. The main safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding. A total of 449 (83%) of the 543 patients could be included in the per-protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and 6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 9.9% of those receiving standard therapy. The main safety outcome occurred in 5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 8.8% of those receiving standard therapy. These results with simple fixed-dose oral regimens justify phase 3 evaluations (www.ClinicalTrials.gov no.NCT00395772).

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Treatment Outcome; Ultrasonography; Venous Thrombosis

Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban.. This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total hip replacement surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6-8 h after surgery) or enoxaparin (40 mg od starting the evening before surgery). Therapy continued until mandatory bilateral venography was performed 5-9 days after surgery.. A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint - deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality - occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationship with rivaroxaban for the primary efficacy endpoint was not statistically significant (p=0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban (p=0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban (p=0.0008), occurring in 0-10.8% of patients, compared with 0% in patients receiving enoxaparin.. This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total hip replacement surgery.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Phlebography; Postoperative Complications; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography.. A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography.. Patients received study drugs until mandatory, bilateral venography was performed 7 +/- 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus.. A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively.. Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs.

Topics: Anticoagulants; Enoxaparin; Hip Prosthesis; Humans; Knee Prosthesis; Morpholines; Orthopedic Procedures; Phlebography; Postoperative Complications; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Ultrasonography; Venous 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

BAY 59-7939, a novel, oral, direct factor Xa inhibitor, is in clinical development for the prevention of venous thromboembolism (VTE), a frequent complication following orthopaedic surgery.. In a multicenter, parallel-group, double-blind, double-dummy study, 621 patients undergoing elective total knee replacement were randomly assigned to oral BAY 59-7939 (2.5, 5, 10, 20, and 30 mg b.i.d., initiated 6-8 h postsurgery), or subcutaneous enoxaparin (30 mg b.i.d., initiated 12-24 h postsurgery). Treatment was continued until mandatory bilateral venography 5-9 days after surgery. The primary efficacy endpoint was a composite of any deep vein thrombosis (proximal and/or distal), confirmed non-fatal pulmonary embolism and all-cause mortality during treatment. The primary safety endpoint was major, postoperative bleeding during treatment.. Of the 613 patients treated, 366 (59.7%) were evaluable for the primary efficacy analysis. The primary efficacy endpoint occurred in 31.7%, 40.4%, 23.3%, 35.1%, and 25.4% of patients receiving 2.5, 5, 10, 20 and 30 mg b.i.d. doses of BAY 59-7939, respectively (test for trend, P = 0.29), compared with 44.3% in the enoxaparin group. The frequency of major, postoperative bleeding increased with increasing doses of BAY 59-7939 (test for trend, P = 0.0007), with no significant difference between any dose group compared with enoxaparin. Bleeding endpoints were lower for the 2.5-10 mg b.i.d. doses compared with higher doses of BAY 59-7939.. Oral administration of 2.5-10 mg b.i.d. of BAY 59-7939, early in the postoperative period, showed potential efficacy and an acceptable safety profile, similar to enoxaparin, for the prevention of VTE in patients undergoing elective total knee replacement.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Arthroplasty, Replacement, Knee; Double-Blind Method; Enoxaparin; Hemorrhage; Humans; Incidence; Injections, Subcutaneous; Male; Middle Aged; Morpholines; 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

Paediatric clinical practice for treatment of venous thromboembolism (VTE) is based on extrapolation from adult trials with minimal data on anticoagulation efficacy and safety in children. Based on EINSTEIN-Jr clinical trial data, rivaroxaban was approved to treat VTE and prevent its recurrence in children of all ages.. To report the safety and efficacy of rivaroxaban use in paediatric VTE and to present real-world data, specifically about very young children.. We conducted a retrospective observational study at Birmingham Children's Hospital. Data were collected from patients <16 years old who received rivaroxaban after its licensure in the period between March 2021 and June 2022.. Rivaroxaban was used for treatment of acute VTE in 64 patients. Thrombosis was CVC-related in 26 patients, unprovoked in 3, while the rest had one or more risk factors for VTE. Safety and efficacy of rivaroxaban were assessed in 52 patients after excluding patients who were on current rivaroxaban treatment and those who were lost to follow up or stopped rivaroxaban due to intolerance. No bleeding events were reported, and recurrence of thrombosis occurred in only 3.6 %. About 35 % had normalised re-imaging, 40.3 % improved, 9.6 % were unchanged and 11.5 % stopped rivaroxaban without re-imaging. Rivaroxaban was used for secondary VTE prophylaxis in 6 patients in our cohort with no recurrence of thrombosis or bleeding reports.. Our real-world experience confirmed that rivaroxaban was well tolerated, effective and safe. Further real-world data and observational studies are essential to investigate the use of rivaroxaban among different risk groups.

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Porto-mesenteric venous thrombosis (PMVT) is a significant complication that occurs more frequently after laparoscopic sleeve gastrectomy (SG) than other bariatric procedures and presents later than other venous thromboembolic (VTE) events often 2 weeks after the operation. The common current practice in bariatric surgery of perioperative chemoprophylaxis until discharge may not adequately prevent PMVT. Therefore, a 30-day post-discharge chemoprophylaxis (PDC) might reduce the incidence of PMVT. The objective of this study is to determine whether 30-day PDC with rivaroxaban 10 mg daily following SG can reduce the incidence of PMVT.. In a retrospective cohort study, 292 consecutive patients undergoing SG by a single surgeon were either prescribed rivaroxaban 10 mg daily for 30 days upon discharge (group A) or did not receive any PDC (group B). Primary outcome was PMVT and secondary outcome was bleeding. Patients on chronic anticoagulation therapy were excluded from the study.. PMVT events differences were significant between the groups while bleeding events were not. Group A had zero PMVT events, while group B had four (p = .045). There were 4 bleeding events in group A and 7 bleeding events on group B (p = .341).. A 30-day PDC regimen of rivaroxaban 10 mg daily is both safe and effective. This study demonstrated zero PMVT events without an increased risk of bleeding using this regimen.

Topics: Aftercare; Anticoagulants; Gastrectomy; Humans; Laparoscopy; Mesenteric Ischemia; Obesity, Morbid; Patient Discharge; Portal Vein; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thrombosis

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

Topics: Humans; Rivaroxaban; Venous Thrombosis

The natural history of endovenous glue-induced thrombus (EGIT) resolution and the role of anticoagulation (AC) and/or anti-platelet (AP) agents in their management is currently ill-defined. The goal of this investigation is to determine the clinical behavior of EGITs and whether or not AC or AP affects treatment outcomes.. We performed a retrospective review of all endovenous ablations utilizing cyanoacrylate glue (CAG) from January 2020 to December 2021 at the Center for Vein Restoration. Patients were divided into two groups: (1) patients who developed an EGIT (EGIT/CAG) and (2) patients treated with CAG and no EGIT development (CAG). Demographics, medical/surgical histories, revised Venous Clinical Severity Score (rVCSS), Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ), CEAP, EGIT category, type of anticoagulation, resolution time, location of any deep vein thrombosis (DVT) were analyzed, catheter tip distance, treatment length and proximal thigh diameters were all analyzed. EGITs were categorized as follows: EGIT 1: thrombus extension into the deep vein covering less than 25% of the luminal area; EGIT 2: thrombus between 25% and 49%; EGIT 3: thrombus between 50% and 74%; and EGIT 4: total occlusion. Our protocol is to perform post-procedure duplex scans within 3 to 7 days after endovenous ablations to assess for post-intervention DVTs.. During the study period, 2374 patients received 4321 CAG procedures. EGITs were observed in 133 patients (3.1%): EGIT 1 (n = 57); EGIT 2 (n = 35); EGIT 3 (n = 19); and EGIT 4 (n = 22). All EGITs were identified by surveillance scanning. No patient presented with limb or pulmonary symptoms suggestive of VTE. The average age, rVCSS, and CIVIQ 20 of the entire cohort was 65.3 ± 14.2 years, 8.2 ± 2.8, and 48 ± 18.3, respectively with 89 females and 44 males. For EGIT 1, 56 of 57 (98%) resolved at 4.2 ± 5.1 weeks, with one patient lost to follow-up. AC/AP regimen included two aspirin (ASA), one Eliquis, 5 Xarelto, and nothing in 49 patients (86%). For EGIT 2, 27 of 35 (77%) resolved at 4.4 ± 3.4 weeks, one was unresolved, six regressed to EGIT 1, and one remained an EGIT 2 at the last follow-up examination. AC/AP regimens included seven ASA, three Eliquis, three Xarelto, one Coumadin, and nothing in 21 patients (60%). For EGIT 3, 12 were in the common femoral vein (CFV), three in the popliteal vein (POPV), one in the external iliac vein, and three in the gastrocnemius veins. Nine of nineteen (47%) resolved at 6 ± 5.9 weeks, four regressed, one migrated to the proximal CFV, three became chronic, and two were lost to follow-up. AC/AP regimens included three ASA, three Eliquis, seven Xarelto, and nothing in six patients (32%). AC/AP compared with no AC/AP had no effect on clot resolution (P = .3). Of the 22 EGIT 4, one was in the CFV, two were in the POPV, and 18 (82%) were remote calf vein DVTs (15 gastrocnemius, one peroneal [PV], and three posterior tibial veins [PTVs]). The CFV EGIT became chronic, one POPV resolved, and one was lost to follow-up. For the gastrocnemius clots, five became chronic, eight resolved, and two were lost to follow-up. For the PTV clots, one resolved, one became chronic, and one was lost to follow-up. The PV clot became chronic. AC/AP regimen included four ASA, five Eliquis, six Xarelto, and nothing in seven patients. AC/AP compared with no AC/AP had no effect on clot resolution (P = .9). The average proximal thigh diameter (millimeters, mm), vein length treated (mm), and catheter distance (mm) from the junction were the following: EGIT 1 (5.9 ± 2.4, 37.5 ± 17.6, and 5.2 ± 1), EGIT 2 (5.9 ± 1.7, 38 ± 16.9, 4.79 ± 0.71), EGIT 3 (5.1 ± 2.6, 27.9 ± 16.6, and 5.26 ± 1.4), and EGIT 4 (5 ± 1.7, 29.9 ± 15.8, and 5.39 ± 2.18), respectively. Treatment length alone was significantly shorter in EGIT 3 and 4, compared with EGIT 1 and 2 (P ≤ .05).. Regardless of EGIT class or severity, the majority of EGITs are not associated with clot extension or migration and tend to resolve or regress. For EGIT class 1 and 2 patients, AC or AP therapy is not necessary, as 86% and 60%, respectively, resolved with observation alone by 4 weeks. For EGIT 3, 68% resolved or regressed regardless of AC or AP use. The majority of EGIT 4 were remote calf vein DVTs. EGIT 3 and 4 associated with the saphenofemoral/popliteal junction are rare. When compared with CAG patients, proximal thigh diameters and treatment lengths were larger and longer in EGIT 1 and 2 patients. Catheter proximity to the junction was not associated with a higher incidence of EGIT formation.

Topics: Aged; Anticoagulants; Female; Femoral Vein; Humans; Male; Middle Aged; Quality of Life; Retrospective Studies; Rivaroxaban; Saphenous Vein; Thrombosis; Treatment Outcome; Venous Insufficiency; Venous Thrombosis

Rivaroxaban (RXB), a novel Xa inhibitor having groundbreaking therapeutic potential. However, this drug is associated with few limitations, including its pharmacokinetics related toxicities. Here, we developed RXB-loaded SLNs (RXB-SLNs) to improve its biopharmaceutical profile. Methods: High pressure homogenizer was used to prepare RXB-SLNs, followed by their particle characterization, Transmission electron microscopy (TEM), Dynamic light scattering (DSC), and Powder X-ray diffraction (PXRD) analysis. Beside this, in-vitro, ex-vivo, and in-vivo evaluation, prothrombin time assessment and toxicity was investigated.. RXB-SLNs had their particle size in nano range (99.1 ± 5.50 nm) with excellent morphology and low polydispersity index (0.402 ± 0.02) and suitable zeta potential (-25.9 ± 1.4 mV). The incorporation efficiency was observed around 95.9 ± 3.9%. In-vitro release profiles of the RXB-SLNs exhibited enhanced dissolution (89 ± 9.91%) as compared to pure drug (11 ± 1.43%) after 24 h of the study. PK study demonstrated a seven times enhanced bioavailability of RXB-SLNs when compared with pure drug. Furthermore, RXB-SLNs exhibited an expressive anti-coagulant behavior in human and rat blood plasma. Also, the final formulation exhibited no toxicity after oral administration of the SLNs.. All together, these studies revealed the capability of the SLNs for carrying the RXB with enhanced therapeutic efficacy and no toxicity, most importantly for the treatment of deep vein thrombosis.

Topics: Administration, Oral; Animals; Crystallography, X-Ray; Drug Carriers; Humans; Lipids; Nanoparticles; Particle Size; Rats; Rivaroxaban; Venous Thrombosis

BACKGROUND Direct oral anticoagulant (DOAC) agents, such as rivaroxaban, treat and prevent venous thrombosis. Although adrenal hemorrhage due to DOACs has previously been reported, this is a rare condition that can present as an emergency. In this case report, we present a 65-year-old man who recently had bilateral knee arthroplasty and was started on rivaroxaban 10 mg daily for deep vein thrombosis (DVT) prophylaxis following the surgery. CASE REPORT Ten days after bilateral knee arthroplasty and starting rivaroxaban, the patient presented to the Emergency Department with severe, sudden abdominal pain. Abdominal computed tomography detected significantly enlarged bilateral adrenals, with ill-defined heterogeneous density extending to the upper part of perinephric and paranephric spaces, suggesting bilateral adrenal hemorrhage. A cosyntropin stimulation test was used to confirm the suspicion of adrenal insufficiency. Cortisol levels were 66 nmol/L before stimulation and 83 nmol/L 60 min after cosyntropin administration. Hydrocortisone was started intravenously at a dose of 50 mg every 8 h. After his symptoms improved, he was discharged on oral hydrocortisone at 10 mg in the morning and 5 mg in the evening. Seven weeks after discharge, follow-up abdominal ultrasonography showed that the bilateral adrenal hemorrhage had resolved. CONCLUSIONS This case supports previous cases of adrenal hemorrhage as a rare but serious association with rivaroxaban and highlights the importance of rapid diagnosis using imaging and monitoring of patients for this possible adverse effect. Practitioners must remain vigilant when prescribing anticoagulation therapy, especially in patients who are at an increased risk for adrenal hemorrhage.

Topics: Aged; Anticoagulants; Cosyntropin; Hemorrhage; Humans; Hydrocortisone; Male; Rivaroxaban; Venous Thrombosis

New oral anticoagulants (NOACs) have been becoming prevalent in recent years and are increasingly used in the treatment of port vein thrombosis. The difference of the efficacy and safety between rivaroxaban and dabigatran remains unclear in the treatment of cirrhotic patients with acute portal vein thrombosis (PVT).. This retrospective study included all consecutive cirrhotic patients with acute portal vein thrombosis in our institute from January 2020 to December 2021. The patients received oral anticoagulation with rivaroxaban or dabigatran. The demographic, clinical, and imaging data of patients were collected. The diagnosis of acute PVT was confirmed by imaging examinations. The severity of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion), liver function, bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).. A total of 94 patients were included, 52 patients (55%) received rivaroxaban and 42 (45%) with dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There was no significant difference in complete recanalization, partial recanalization, and persistent occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI 1.036-1.311, p = 0.011) was independent predictors of complete recanalization. The Child-Pugh score (p = 0.001) was significantly improved in both two groups after anticoagulation, respectively. However, there was no difference between the two groups. The probability of survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p = 0.830). Major bleedings were reported in 3 patients (6%) in rivaroxaban group and 1 patient (2%) in dabigatran group (p = 0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five (12%) from dabigatran group (p = 0.691).. The efficacy and safety were comparable between rivaroxaban and dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis. And D-dimer can contribute to the prediction of PVT recanalization in cirrhotic patients.

Topics: Administration, Oral; Anticoagulants; Dabigatran; End Stage Liver Disease; Hemorrhage; Humans; Liver Cirrhosis; Portal Vein; Retrospective Studies; Rivaroxaban; Severity of Illness Index; Treatment Outcome; Venous Thrombosis

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

Monitoring of direct oral anticoagulants (DOACs) with calibrated anti-Xa assay is limited by the high intra- and interindividual variations of the test results. Thrombin generation (TG) is a global hemostatic assay that reflects the patient´s individual coagulation status. The aim of this study was to investigate the influence of DOACs on TG measured with a fully automated assay system.. All consecutive patients under apixaban and rivaroxaban coming to the outpatient coagulation center MVZ Limbach, Magdeburg, Germany between October 2017 and April 2020 were included. DOAC plasma levels were correlated with TG assessed using the fully automated Ceveron TG analyzer.. A total of 703 rivaroxaban and 252 apixaban containing plasma samples were included. There was a significant correlation between DOAC plasma levels and all TG parameters except for lag time regarding apixaban. Time to peak and peak thrombin followed an exponential regression curve, while this was linear for the endogenous thrombin potential (ETP). Apixaban showed a lower correlation coefficient for all TG parameters compared with rivaroxaban, and thrombin generation was less influenced by apixaban than rivaroxaban at plasma levels >100 ng/ml. The sensitivity and negative predictive value of normal TG parameters for the prediction of DOAC plasma levels <30 ng/ml was >85%.. The present data show a moderate predominantly nonlinear correlation between TG parameters and plasma levels of apixaban and rivaroxaban. Rivaroxaban has a stronger effect on TG than apixaban.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; ROC Curve; Thrombin; Venous Thrombosis

Rivaroxaban use for inferior vena cava (IVC) thrombosis after successful catheter-directed thrombolysis (CDT) is rarely reported. This study aimed at investigating the safety and efficacy of rivaroxaban for IVC thrombosis after CDT. The clinical data on 38 consecutive patients with IVC thrombosis (68% male; mean age, 51.5 ± 16.5), who received rivaroxaban after CDT between July 2017 and January 2020, were retrospectively analyzed in this study. Safety and efficacy of rivaroxaban (bleedings and recurrent venous thromboembolism), cumulative prevalence of post-thrombotic syndrome (PTS), primary patency, clinically driven target lesion revascularization rate, and other adverse events including all-cause mortality and vascular events (systemic embolism, acute coronary syndrome, ischemic stroke, and transient ischemic attack) were retrospectively analyzed. Of the 38 patients who received rivaroxaban for IVC thrombosis after CDT, 27 (71%) had an anticoagulant duration of 6 months and 11 patients (29%) of more than 6 months. Four patients (10%) suffered recurrent thrombosis. No patient suffered major bleeding, while clinically relevant nonmajor bleeding occurred in two (5%) patients. The cumulative prevalence of PTS was 18% (7/38) during the 12 months follow-up period. Primary patency at 1, 3, 6, and 12 months was 97, 92, 90, and 90%, respectively. According to follow-up data, the clinically driven target lesion revascularization of this study was 10%. Cardiovascular events and mortality did not occur in any patient during the study period. Rivaroxaban for IVC thrombosis after successful CDT can be safe and effective.

Topics: Adult; Aged; Catheters; Female; Humans; Male; Middle Aged; Postthrombotic Syndrome; Retrospective Studies; Rivaroxaban; Thrombolytic Therapy; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis

Rivaroxaban, as a novel oral anticoagulant agent, emerged in thrombosis management. This study aimed to compare the efficacy and safety of once-daily rivaroxaban versus dose-adjusted warfarin for cerebral venous thrombosis treatment in a real-world clinical setting. This is a prospective cohort study based on the real-world clinical data analysis of the patients with imaging-confirmed CVT enrolled from August 2016 through January 2020 and their outcomes were followed up. Patients were grouped according to their treatment strategies: rivaroxaban (15-20 mg daily) or warfarin (dosage-adjusted according to international normalized ratio), which were matched 1:2 on the propensity score. The primary efficacy outcome was recanalization assessed by magnetic resonance venography. Thrombus burden, CVT recurrence and modified Rankin Scale (mRS) were also compared. The safety outcome was major bleeding. Baseline characteristics were well balanced between the 33 patients in rivaroxaban group and 49 in warfarin group after propensity score matching. During 6-month (median) follow-up, 29 patients (87.9%) in rivaroxaban group and 38 patients (77.6%) in warfarin group obtained recanalization (OR, 1.44; 95% CI 0.63-3.30). The thrombus reduction at the 6-month follow-up did not reach statistical difference (p = 0.118). No CVT recurrence was observed in both groups. All patients in rivaroxaban group obtained favorable functional outcomes (mRS = 0-2), whereas in warfarin group, 1 patient remained physically disable (mRS = 3) at the follow-up. No major bleeding events occurred in two groups. Rivaroxaban might have the same or stronger efficacy in facilitating CVT recanalization and preventing CVT recurrence with a lower incidence of bleeding than that of warfarin in Chinese population.

Topics: Anticoagulants; Hemorrhage; Humans; Intracranial Thrombosis; Prospective Studies; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

Rivaroxaban is an oral anticoagulant that inhibits thrombin and blocks coagulation cascade through directly inactivating factors Xa. Despite rivaroxaban is widely used for prevention and treatment of venous thrombosis, and its common adverse reactions have been reported, including abnormal coagulation, mucosal hemorrhage, hematuria, and intracranial hemorrhage. To explore potential drivers of individual differences in adverse reactions induced by rivaroxaban, we performed whole-exome sequencing and found that AKR7A3 rs1738023/rs1738025 and ABCA6 rs7212506 are susceptible sites for rivaroxaban-related bleeding in aged patients treated with rivaroxaban. Gene functional annotation and signaling pathway enrichment indicated that homozygous mutations in AKR7A3 and ABCA6 might alter normal rivaroxaban transport and metabolism, and lead to continuous accumulation of activated drugs and toxic substances in vivo. Our results suggested that interindividual differences in bleeding events induced by rivaroxaban may be potentially driven by genetic alterations related to abnormal metabolism and transport of rivaroxaban.

Topics: Aged; Anticoagulants; ATP-Binding Cassette Transporters; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Venous Thrombosis

 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

We aimed to describe the clinical presentation, risk of bleeding and recurrent thrombosis, and perioperative anticoagulant management of children with cerebral venous thrombosis (CVT) and an associated head or neck infection.. In this subgroup analysis of the EINSTEIN-Jr study, we included children with CVT and an associated head or neck infection who received therapeutic anticoagulants with either low-molecular-weight heparin (with or without subsequent vitamin K antagonists) or rivaroxaban for a period of 3 months. Analyses are descriptive.. Of 74 included children, 59 (80%) had otomastoiditis, 21 (28%) a central nervous system infection, 18 (24%) sinusitis, and 9 (12%) another upper respiratory tract infection; 29 (39%) had infection of multiple regions of the head or neck. All 74 children received antibiotics and therapeutic anticoagulants; 41 (55%) underwent surgery, of whom 34 were diagnosed with CVT preoperatively. Anticoagulation was started before surgery in 12 children and interrupted 0-1 days prior to surgery. Anticoagulation was (re)started in all 34 children at a median of 1 day (interquartile range: 0-1) postoperatively, in therapeutic doses in 94%. Overall, one child (1%, 95% confidence interval: 0-7) had recurrent thrombosis, and one (1%, 95% confidence interval: 0-7) had major bleeding; neither was associated with surgery. At 3 months, no children had died, 3 (4%) had persistent focal neurologic deficits, and 2 (3%) had impaired vision.. Children with CVT and an associated head or neck infection administered therapeutic anticoagulants generally had low risks of bleeding and thrombotic complications, including those who had surgical interventions with delay or interruption of anticoagulation.

Topics: Anticoagulants; Central Nervous System Infections; Child; Child, Preschool; Cohort Studies; Female; Heparin, Low-Molecular-Weight; Humans; Intracranial Thrombosis; Male; Mastoiditis; Rivaroxaban; Sinusitis; 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

Regression of thrombus in response to treatment with direct oral anticoagulants (DOACs) in patients with extensive deep vein thrombosis (DVT) has not been fully evaluated. This study aimed to determine the therapeutic efficacy of rivaroxaban in the treatment of extensive DVT.. We retrospectively evaluated 76 patients treated with rivaroxaban among 728 new DVT patients, at our hospital from January 2018 to March 2021. Extensive DVT was defined as thrombus connecting to 2 or more segments of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. Localized DVT was defined as a thrombus confined to 1 segment of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. We compared the changes in thrombus between the extensive DVT group (36 patients) and the localized DVT group (40 patients).. In the localized DVT group, 14 (37%) had total recanalization within 3 weeks after DOAC initiation, and 30 (79%) had total recanalization within 3 months. In the extensive DVT group, only 3 (9%) had total recanalization within 3 weeks after starting DOAC, and even after 3 months, only 5 (15%) had total recanalization. Symptoms (P = 0.01) and extensive DVT (P < 0.01) were significantly associated with the risk for failure of total recanalization.. Rivaroxaban was highly effective for total recanalization of localized DVT but not for symptomatic or extensive DVT. In patients with symptomatic extensive DVT, catheter-based thrombolysis may be considered in selected cases.

Topics: Anticoagulants; Humans; Iliac Vein; Retrospective Studies; Rivaroxaban; Thrombolytic Therapy; Thrombosis; Treatment Outcome; Venous Thrombosis

To explore the cohort study of rivaroxaban combined with D-dimer dynamic monitoring in the prevention of deep venous thrombosis (DVT) after knee arthroplasty.. Eighty-four patients with knee osteoarthritis who went through total knee arthroplasty from June 2019 to June 2021 in our hospital were arbitrarily assigned into the study group and the control group. The patients in the control group were cured with rivaroxaban anticoagulation after operation, and the study group was cured with dynamic monitoring of D-dimer on the basis of the control group. The incidence of postoperative DVT, pulmonary embolism (PE), and bleeding complications (incision ecchymosis and bleeding events) were compared. The related indexes such as drainage volume and blood transfusion volume were compared. The levels of activated partial prothrombin time (APPT), prothrombin time (PT), and D-dimer were dynamically monitored before and after operation. Visual analogue scale (VAS) was adopted to assess the degree of postoperative incision pain, the level of limb swelling before and after operation was measured, the circumference difference of affected limb was calculated, the ecchymosis area was assessed in the form of nine-palace grid, and the scores were compared.. According to the comparison of VAS score, there exhibited no remarkable difference before operation and on the first day after operation, but the VAS score decreased after operation, and the VAS score of the study group on the 3rd day, 7th day, and 14th day after operation was remarkably lower compared to the control group (. Rivaroxaban combined with D-dimer dynamic monitoring has high clinical value in preventing DVT after knee arthroplasty and can effectively reduce the amount of blood loss during operation and the incidence of postoperative DVT, PE, and bleeding complications, which is worth popularizing to reduce the area of ecchymosis and the degree of pain after operation and shorten the recovery process.

Topics: Arthroplasty, Replacement, Knee; Cohort Studies; Ecchymosis; Fibrin Fibrinogen Degradation Products; Humans; Pain; Postoperative Complications; Rivaroxaban; Venous Thrombosis

To study the efficacy and safety of percutaneous mechanical thrombectomy and long-term anticoagulation with rivaroxaban for proximal deep vein thrombosis.. We analyzed the effectiveness of treatment in 60 patients with proximal deep vein thrombosis divided into 2 homogeneous groups by 30 people. Standard therapy was performed in the first group, therapy with percutaneous mechanical thrombectomy was applied in the second group. Patients received rivaroxaban in preoperative, perioperative and 6-month postoperative period. We considered complications of endovascular treatment and anticoagulation. Ultrasound and clinical examination were carried out after 12 months to analyze restoration of deep vein patency and venous outflow disorders. Recovery of vein lumen was assessed as follows: <50% - minimal, 50-99% - partial, 100% - complete.. Recurrent deep vein thrombosis was found in 2 (6.7%) patients of the second group. Hemorrhagic complications following rivaroxaban therapy occurred in 8 (13.3%) patients (equally in both groups). In the first group, complete restoration of vein lumen was found in 16.7% of patients, partial recovery - in 40%, minimal recovery - in 43.3% of patients. In the second group, these values were 16.7%, 60% and 23.3%, respectively. Severe venous outflow impairment developed in 43.3% of patients in the first group and 23.3% of patients in the second group. Moderate impairment occurred in 30% and 20% of patients, mild disorders - in 10% and 40% of patients, respectively.. Percutaneous mechanical thrombectomy on the background of long-term anticoagulation with rivoroxaban improves treatment outcomes in patients with proximal deep vein thrombosis.. Изучить эффективность и безопасность чрескожной механической тромбоэкстракции и длительной антикоагулянтной терапии ривароксабаном при лечении проксимального тромбоза глубоких вен нижних конечностей.. Проведен анализ эффективности лечения 60 больных с проксимальным тромбозом глубоких вен, разделенных на 2 статистически однородных группы по 30 человек. Пациентам 1-й группы проводили стандартное консервативное лечение, 2-й группы — такое же консервативное лечение, дополненное чрескожной механической тромбэктомией. До, во время и в течение 6 мес после операции больные получали ривароксабан. Во время лечения регистрировали осложнения эндоваскулярной и антикоагулянтной терапии. Через 12 мес проведено контрольное ультразвуковое и клиническое обследование больных для выявления степени восстановления просвета глубоких вен и выраженности нарушения венозного оттока. Восстановление просвета вен оценивали следующим образом: <50% — минимальное, 50—99% — частичное, 100% — полное.. Ретромбоз глубоких вен обнаружен у 2 (6,7%) больных во 2-й группе, геморрагические осложнения после приема ривароксабана — у 8 (13,3%): в обеих группах поровну. В 1-й группе полное восстановление просвета вен установлено у 16,7% больных, частичное — у 40%, минимальное — у 43,3%, во 2-й группе — соответственно у 16,7, 60 и 23,3%. Сильная степень выраженности нарушения венозного оттока развилась в 1-й группе у 43,3% больных, во 2-й —у 23,3%, средняя степень — соответственно у 30 и 20%, слабая — у 10 и 40%.. Чрескожная механическая тромбоэкстракция на фоне длительного применения ривороксабана позволяет улучшить результаты лечения больных с проксимальными тромбозами глубоких вен нижних конечностей.

Topics: Anticoagulants; Humans; Retrospective Studies; Rivaroxaban; Thrombectomy; Thrombolytic Therapy; Treatment Outcome; Venous Thrombosis

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

Empiric anticoagulation therapy is often used in patients with suspected deep vein thrombosis (DVT) to avoid complications if the workup is delayed. Studies have shown the safety of administering direct oral anticoagulants (DOACs) and low molecular weight heparin in patients with suspected DVT. However, the impact of empiric DOACs on D-dimer levels in patients with suspected DVT is not well established. Therefore, this study aimed to determine the effect of empiric rivaroxaban on the diagnostic performance of D-dimer.. D-dimer was measured before and after the administration of one to two tablets of rivaroxaban in 418 patients referred with suspected DVT to the Emergency Department at Østfold Hospital, Norway. To determine whether the effect of rivaroxaban significantly impacted D-dimer results, we calculated the diagnostic performance of the test before and after patients had taken rivaroxaban. All patients with negative workup were followed up at 90 days.. Two hundred eighty-six (68.4 %) of the 418 included patients had lower D-dimer results after taking rivaroxaban. Median D-dimer values decreased from 1.0 mg/L (IQR: 0.7-2.2) to 0.9 mg/L (IQR: 0.6-2.0). Thirty-six patients (8.9 %) with positive D-dimer (≥ 0.5 mg/L fibrinogen-equivalent units) before taking rivaroxaban had negative D-dimer values after rivaroxaban intake. Of these, two had DVT diagnosed by compression ultrasonography. The sensitivity of D-dimer decreased from 99.0 % (95 % CI: 94.6-99.8) to 97.0 % (95 % CI: 91.6-99.0).. Rivaroxaban administered before measuring D-dimer may reduce the sensitivity and increase false negative results of the test. Based on these results, we recommend performing D-dimer before the administration of rivaroxaban.

Topics: Anticoagulants; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Predictive Value of Tests; Rivaroxaban; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Embolism; Factor Xa Inhibitors; Humans; Obesity; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Gastric carcinoma (GC) is a common lethal cancer in the world. Patients are prone to develop lower extremity deep venous thrombosis (LEDVT) after laparoscopic radical gastrectomy (LRG), which threatens their life and health.. This research is to clarify the preventive action of rivaroxaban (Riv) against LEDVT in patients undergoing LRG.. A retrospective study was conducted on 70 patients with GC admitted for LRG between January 2019 and January 2022, including 40 patients (observation group) receiving Riv treatment and 30 patients (conventional group) treated with air wave pressure therapy apparatus. Quality of life, coagulation function, LEDVT formation, and complications were compared between groups.. The observation group had better recovery of life quality than the control group, along with more effective inhibition of coagulation disorders, less DVT formation, and fewer complications.. Compared with air wave pressure therapy apparatus, Riv has better preventive action against LEDVT in GC patients after LRG.

Topics: Gastrectomy; Humans; Laparoscopy; Lower Extremity; Quality of Life; Retrospective Studies; Rivaroxaban; Stomach Neoplasms; Venous Thrombosis

Venous thromboembolic disease (VTD) is currently the second leading cause of death in cancer patients with a prevalence of approximately 20% compared with that of 5% in the entire adult population. Cancer patients are a heterogeneous group with significant differences in the risk of VTD which is, in particular, determined by the type of tumour, its extent, location, and the presence of metastases. Some tumours represent a mean 3- to 5-fold increase in risk, while in others the risk of developing VTD is even several times higher. In comparison with non-cancer patients, those with a tumour are not only at an increased risk of an initial thromboembolic event, but also of its recurrence, regardless of ongoing anticoagulation which is associated with a higher risk of bleeding, particularly in mucosal involvement. Venous thrombosis and its treatment may interfere with the ongoing diagnosis and treatment. In cancer patients, VTD is a frequent incidental finding on imaging studies. Primary thromboprophylaxis (apixaban, rivaroxaban, LMWH) is currently recommended in selected groups of cancer patients who are either hospitalized for acute internal disease or immobilized and have an active malignancy, undergo outpatient systemic chemotherapy for a tumour with a high risk of VTD (a Khorana score of 2) or surgery and are not at high risk of bleeding. DOACs should be administered six months after the initiation of chemotherapy. If there is a risk of drug interactions or mucosal bleeding, LMWHs are recommended. At present, DOACs (apixaban, edoxaban, rivaroxaban) and LMWHs are the first-choice drugs in treating VTD. LMWHs are preferred in mucosal tumours, when there is a high risk of bleeding, in progressive malignancy, concomitant emetogenic therapy, and dyspeptic difficulties. In severe renal insufficiency (CrCl < 15 ml/min), vitamin K antagonists may be of value. Individualized treatment should take into consideration the patients general condition, prognosis, and personal preferences.

Topics: Administration, Oral; Adult; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Vitamin K

BACKGROUND Two Pediatric Patients with Splanchnic Venous Thrombosis as a Complication of Acute Pancreatitis Successfully Treated with Low-Molecular-Weight Heparin and Rivaroxaban CASE REPORT Case 1: A 13-year-old girl presented with a second attack of acute pancreatitis. She developed a non-occlusive splenic vein thrombosis diagnosed by CT scan on the sixth day of hospitalization. Injectable low-molecular-weight heparin was started during hospitalization and switched to oral rivaroxaban at discharge. Imaging at follow-up showed resolution of thrombosis. Case 2: A 9-year-old girl with history of acute recurrent pancreatitis presented with a third attack of acute pancreatitis. An occlusive splenic vein thrombosis with extension into the portal vein and superior mesenteric vein and necrotizing pancreatitis was seen on CT scan on the third day of hospitalization. Low-molecular-weight heparin was initiated during hospitalization and was switched to oral rivaroxaban at discharge. Imaging at follow-up demonstrated nearly complete resolution of the extensive thrombosis. CONCLUSIONS Splanchnic venous thrombosis remains a rare complication of pediatric pancreatitis. Anticoagulant use in patients with these complications remains controversial. Direct oral anticoagulants are as safe and effective as low-molecular-weight heparin and should be considered for use in children instead of low-molecular-weight heparin due to its advantages, including the availability of enteral forms of administration.

Topics: Acute Disease; Adolescent; Anticoagulants; Child; Female; Heparin, Low-Molecular-Weight; Humans; Pancreatitis; Rivaroxaban; Splenic Vein; Thrombosis; Venous Thrombosis

Protein S is a vitamin K-dependent protein that acts as a break in secondary hemostasis by inactivating activated factor V and activated factor VIII. We report a case of a 40 years old male who had the first episode of deep vein thrombosis of the left lower limb 10 years back, which despite treatment, reoccurred 3 months later in the bilateral lower limb. Thrombophilic screening showed severe protein S deficiency. The patient then developed deep vein thrombosis of both upper limbs. The patient was advised to place an inferior vena cava filter, which he denied. The patient is now presenting with multiple episodes of post-thrombotic syndrome. Such attacks are treated with elastic compression stockings, rivaroxaban, and morphine. However, despite medication, the pain has not yet subsided. Hence, even though protein S deficiency is the rare cause of deep vein thrombosis when recurrent should be considered despite its rare occurrence.. deep vein thrombosis; protein S deficiency; rivaroxaban.

Topics: Adult; Humans; Male; Postthrombotic Syndrome; Protein S Deficiency; Rivaroxaban; Venous Thrombosis; Vitamin K

The acute vascular disease deep vein thrombosis (DVT) requires oral anticoagulants to prevent progression. Monitoring therapeutic efficacy of direct oral anticoagulants (DOAC), including rivaroxaban, is problematic as no reliable test is available. Advances in rheometry have led to the development of a functional coagulation biomarker using Gel Point (GP) analysis which assesses clot structure formation. The biomarker measures incipient clot formation time (TGP) and quantifies fibrin clot structure in terms of fractal dimension (df).. This study aimed to investigate clot structure formation in first time DVT and the effect of rivaroxaban treatment.. This prospective observational cohort study measured the GP and standard laboratory markers at three sample points: pre-treatment and at 20 and 60 days following 15 mg BD and 20 mg OD rivaroxaban respectively.. Forty DVT patients (mean age 64 years [SD±14.8]; 23 males, 17 female) were recruited. The results show that DVT vs non-DVT patients did not have a significantly different GP profile (df: 1.72±0.06 vs 1.70±0.06 and TGP: 267±68 sec vs 262±73 sec) with both within the defined healthy index. In addition, rivaroxaban therapy increased TGP to 392 s (±135 s) after 20 days, and subsequently increased to 395 s (±194 s) at 60 days but did not significantly increase df (from 1.69±0.05 to 1.71±0.06).. The results indicate in this cohort of DVT patients there was no underlying hypercoagulable effect as determined by gel point analysis. Furthermore, the anticoagulant effect of rivaroxaban prolonged clotting, suggesting a protective effect against clot formation, without significantly reducing clot microstructural properties.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Female; Humans; Male; Middle Aged; Prospective Studies; Rivaroxaban; Venous Thrombosis

The mainstay of cerebral venous thrombosis (CVT) treatment according to current guidelines is parenteral anticoagulation with unfractionated heparin or low-molecular-weight heparin followed by long-term oral anticoagulation with vitamin K antagonists. Direct oral anticoagulants (DOACs), including the factor Xa inhibitor rivaroxaban, are used occasionally off-label for CVT based on individual treatment plans. This publication sought to report our experience with rivaroxaban for the indication of CVT and to review the relevant literature data concerning this topic. We performed a single-center retrospective analysis including patients from our institution with the diagnosis of cerebral venous thrombosis treated with rivaroxaban. Among 12,500 stroke patients over an 11-year period, we identified 87 cases with a diagnosis of CVT (0.7%). As long-term anticoagulation, 80 of these patients were receiving vitamin K antagonists and seven were receiving DOACs, including six receiving rivaroxaban and one receiving apixaban. Of the six patients receiving rivaroxaban, at least 6 months of clinical follow-up data were available for five of them. Excellent clinical outcomes were obtained in four of these five cases (modified Rankin scale score: 0-1 points). No hemorrhagic events, recurrent thrombosis, or other relevant complications were recorded during the follow-up period. Despite our small study sample size, our positive results support that rivaroxaban may be a safe and effective treatment option for patients with CVT. Hopefully, ongoing randomized clinical trials will better clarify the role of rivaroxaban in the treatment of CVT so as to provide a more convenient and safer alternative to vitamin K antagonists in this context.

Topics: Aged; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Young Adult

Topics: Disease Management; Factor Xa Inhibitors; Humans; Rivaroxaban; Treatment Outcome; Venous Thrombosis

Topics: Anticoagulants; Child; Dabigatran; Disease Management; Humans; Rivaroxaban; Venous Thrombosis

Venous thrombosis remains a significant problem in modern days. Genetic factors contribute to a subset of patients with venous thrombosis. It is sometimes challenging to identify the underlying culprit in thrombophilic individuals based on traditional laboratory testing and Sanger sequencing.. A thrombophilic family presented with multiple venous thrombosis was examined.. Molecular genetic analysis revealed a pathogenic missense variant of the PROS1 gene. Based on this finding and clinical manifestations, a final diagnosis of protein S deficiency was made.. Whole exome sequencing (WES) of the proband was performed to identify disease-causing variants. Subsequently, Sanger sequencing was performed to validate the variant in the affected members.. Using WES, we rapidly identified a proven pathogenic missense variant (c.1543C > T, p.Arg515Cys) in the sex hormone-binding globulin domain of PROS1, which was confirmed by Sanger sequencing. The decreased level and activity of protein S caused by the variant explained the phenotypes of the family. Patients received rivaroxaban as a long-term anticoagulation therapy and achieved a good prognosis.. Our study suggests WES as a rapid search strategy to identify the genetic factors underlying thrombophilic disorders. Patients with venous thrombosis caused by PROS1 mutations could receive rivaroxaban as the first choice of anticoagulation therapy.

Topics: Adult; Anticoagulants; Exome Sequencing; Factor Xa Inhibitors; Humans; Male; Pedigree; Protein S; Rivaroxaban; Venous Thrombosis

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Ischemic Attack, Transient; Pulmonary Disease, Chronic Obstructive; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism; Venous Thrombosis

Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA.. This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded.. Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09).. Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.

Topics: Acenocoumarol; Adult; Anticoagulants; Budd-Chiari Syndrome; Duration of Therapy; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Mesenteric Ischemia; Middle Aged; Portal Vein; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thrombosis; Warfarin

Isolated distal deep-vein thrombosis (DVT, infra-popliteal DVT without pulmonary embolism) is a common presentation of venous thromboembolism (VTE), but was an exclusion criterion from the pivotal trials that validated the use of direct oral anticoagulants (DOACs) for VTE management. Using data from the international RIETE registry, we analyzed and compared trends in DOACs prescription between January 2011 and June 2019 in patients with distal vs. proximal DVT. We also assessed DOACs' prescriptions and compared the outcomes (VTE recurrence, bleeding and death) of distal DVT patients treated with DOACs vs. those on vitamin K antagonists (VKAs). 2308 patients with distal DVT and 11,364 patients with proximal DVT were included in the current analysis. DOACs were more frequently prescribed in patients with distal than proximal DVT (25% vs. 16%, p < 0.001). DOACs use increased sharply during the observation period (P < 0.001 for trend). In 2018, 56% of patients with distal DVT received DOACs. Distal DVT patients treated with rivaroxaban or edoxaban received the dose recommended for VTE management in most (> 85%) cases. Patients treated with apixaban were older, more likely to have underlying conditions than patients treated with rivaroxaban and, in most cases (> 75%), did not receive the recommended 1-week loading dose for acute VTE management. Outcomes between distal DVT patients treated with VKAs or DOACs appeared to be similar. In patients with distal DVT, DOACs have become the most common anticoagulant regimen. Specific trials are needed to determine the optimal DOACs dose regimen for treatment of distal DVT.

Topics: Administration, Oral; Anticoagulants; Humans; Registries; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

To explore the clinical and prognostic features of CVT caused by PROS1 gene mutations and to provide clinical experience for new oral anticoagulants, such as rivaroxaban, in the treatment of CVT with a high risk of thrombosis.. The CVT patient's clinical symptoms were described, and the brain imaging and blood coagulation tests were performed to confirm the diagnosis of CVT. The patient's family members were recruited to receive blood coagulation tests and ultrasonic examination of lower limb vessels. Genetic analysis on the pedigree was carried out to identify the responsible gene for PS deficiency. We followed-up with this patient for 24 months to evaluate the clinical outcomes, laboratory results and imaging performances of CVT.. The patient presented with typical CVT symptoms, including headache and epilepsy. Brain CT showed hemorrhage in the bilateral frontal lobe and left occipital lobe, while MRV demonstrated that thrombus had occurred. It was reviewed that the patient and his mother had a history of bilateral leg deep vein thrombosis. Gene tests revealed that the patient and two family members carried a heterozygous mutation of PROS1 (c.751_752delAT, p.M251Vfs*17). During 24 months of follow-up study, the patient was treated with rivaroxaban continuously and recovered well, supported by an mRS score that remained below 2. Blood coagulation tests were within normal limits, and MRV revealed partial recanalization of the cerebral venous sinus.. The frame shift mutation in the PROS1 gene (c.751_752delAT) may greatly affect the function of protein S and lead to a severe phenotype of CVT. Rivaroxaban showed a satisfying therapeutic effect in this CVT patient with hereditary thrombophilia.

Topics: Administration, Oral; Adult; Anticoagulants; Blood Coagulation; Follow-Up Studies; Humans; Male; Mutation; Pedigree; Protein S; Protein S Deficiency; Rivaroxaban; Thrombophilia; Venous Thrombosis

New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events due to their lower bleeding risk. There is a lack of evidence on the effectiveness and safety of Rivaroxaban in Cerebral venous thrombosis (CVT). This study aims to assess the effectiveness and bleeding risk of Rivaroxaban in comparison with Warfarin for the treatment of CVT.. 36 patients with diagnosis of CVT were included. Clinical and background information was assessed on admission and patients were followed for at least 12 months. Measured outcomes were modified Rankin Scale (mRS), evidence of recanalization on contrast-enhanced Brain MR venography (MRV) and major or minor bleeding. Patients were divided into two groups according to the type of oral anticoagulant (Rivaroxaban vs Warfarin). Groups were compared in terms of final outcomes and side effects.. Overall, 13 (36.11%) patients received Warfarin and 23 (63.89%) received Rivaroxaban. Optimal mRS score (0-1) was attained in 9 of 10 (90%) of patients treated with Rivaroxaban and 19 of 22 (86.36%) of patients received Warfarin. MRV showed complete or partial recanalization in 12 of 14 (85.71%) patients treated with Rivaroxaban and all patients in the Warfarin group. There was no significant difference between the two groups in terms of major and minor hemorrhage.. Rivaroxaban holds promise for the treatment of CVT.

Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

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

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Ascites; C-Reactive Protein; Cholecystitis, Acute; Delayed Diagnosis; Dementia; Factor Xa Inhibitors; Female; Humans; Portal Vein; Rivaroxaban; Sulbactam; Tomography, X-Ray Computed; Ultrasonography; Venous Thrombosis

In ambulant patients with lower limb DVT managed with Warfarin, there is a need for initial treatment and short time "bridging" with a rapidly acting anticoagulant until there is a stable therapeutic INR. In this study, results from bridging with subcutaneous low molecular weight heparin (LMWH) or oral Rivaroxaban were compared.. One hundred and twenty-four patients received LMWH and 98 patients received Rivaroxaban, both in addition to Warfarin. Patients were assessed at 1 and 4 weeks after treatment initiation for thrombus progression, bleeding, clinic attendance and INR.. The treatment groups were well matched. There were no significant differences between the treatment groups for any of the end-points at either 1 week or 4 weeks.. In ambulant patients with DVT treated with Warfarin both Rivaroxaban and LMWH are suitable for use in the early phase of Warfarin treatment until therapeutic INR is achieved. Rivaroxaban is a suitable alternative to LMWH for patients who prefer not to have injections.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Venous Thrombosis; Warfarin

We reported an anaphylactic reaction following ingestion of rivaroxaban in a 48-years-old male, who was recently discharged from the hospital as a case of deep vein thrombosis. At home, the patient developed a diffuse itchy skin rash, shortness of breath, and vomiting 30 minutes after rivaroxaban ingestion. Emergency Medical Service found that the patient had severe dyspnea, low blood pressure, and decreased blood oxygen saturation. The patient was given oxygen, intramuscular epinephrine, intravenous hydrocortisone, diphenhydramine, salbutamol nebulizer, and was immediately transferred to the emergency department of Hamad General Hospital. Subcutaneous enoxaparin was initiated, while hydrocortisone and salbutamol nebulizer continued. On the next day, his vital signs had stabilized, and intravenous hydrocortisone was switched to prednisolone tablets, and salbutamol nebulizer was switched to budesonide/salmeterol inhaler, whereas enoxaparin was overlapped with warfarin. After achieving the target international normalized ratio (INR), enoxaparin was discontinued and the patient was discharged with significant clinical and laboratory improvement.

Topics: Anaphylaxis; Anticoagulants; Bronchodilator Agents; Factor Xa Inhibitors; Glucocorticoids; Humans; Male; Middle Aged; Rivaroxaban; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Humans; Lower Extremity; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

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

Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Rivaroxaban; Venous Thrombosis; Warfarin

Thrombosis resolution is an important component of treatment for deep vein thrombosis (DVT) and multiple anticoagulants are now available. It is unknown whether rivaroxaban contributes to a higher degree of thrombus resolution compared to conventional anticoagulation with warfarin. Our objective was to compare thrombus resolution for rivaroxaban versus warfarin treated patients with acute lower extremity DVT. Consecutive patients treated for proximal or distal lower extremity DVT with rivaroxaban were identified from the Mayo Thrombophilia Clinic Anticoagulants Registry (November 2015-June 2016) and compared to patients treated with warfarin. Ultrasonography/Doppler images were analyzed by two independent radiologists blinded to anticoagulant and using a standardized assessment algorithm. A total of 111 patients with DVT were studied. Sixty-three rivaroxaban treated patients were compared to 48 warfarin treated patients over a median follow up of 92 and 97 days, respectively. Percentage of patients with total or partial resolution of thrombosis was similar in rivaroxaban and warfarin treated groups (95.2% vs. 91.7%, p = 0.46, respectively); also the proportion of patients with total thrombus resolution was not significantly different (38.1% vs. 29.2%, p = 0.42, respectively). There was no significant difference in the proportion of patients with no thrombus resolution between rivaroxaban and warfarin treated groups either (4.8% vs. 2.1%, p = 0.63). Thrombus propagation with warfarin therapy was observed in 6.3% of patients treated with warfarin and in none of the patients from the rivaroxaban group (p = 0.08). Resolution of acute lower extremity DVT in patients treated with rivaroxaban is similar to those treated with warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Lower Extremity; Male; Middle Aged; Registries; Rivaroxaban; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Rivaroxaban; Venous Thrombosis; Warfarin

Post-thrombotic syndrome (PTS) is a complication of deep vein thrombosis (DVT). Residual vein thrombus (RVT) on Doppler Ultrasound can be associated with PTS. Limited data are available on the effect of direct oral anticoagulants (DOACs) on the long-term outcome of PTS. This study aimed to compare the prevalence of PTS and RVT, in patients with previous DVT treated with rivaroxaban or enoxaparin/warfarin. A total of 129 patients with previous proximal lower limb DVT and treated with rivaroxaban (n = 71) or enoxaparin/warfarin (n = 58) for at least 3 months were included. The Villalta scale for PTS was performed after treatment. The median duration of the DVT symptoms before anticoagulation was 7 days for both groups. The rate of PTS was 50.7% in the patients treated with rivaroxaban and 69% in the enoxaparin/warfarin group. Enoxaparin/warfarin showed an increased prevalence of PTS (P = .018). An analysis in 3 different models showed that the relative risk of PTS decreased by 76% with rivaroxaban use when compared with enoxaparin/warfarin treatment. In addition, 93 of the 129 patients were evaluated regarding the presence of RVT, of which, 11 (24.4%) and 31 (64.6%) presented with RVT for rivaroxaban and enoxaparin/warfarin, respectively (P < .0001). The RVT analysis excluded the possibility of RVT as a mediator of the association between type of treatment and PTS when comparing rivaroxaban with enoxaparin/warfarin (odds ratio (OR) = 0.14; 95% confidence interval (CI): 0.1-1.0, P = .051) with rivaroxaban compared with enoxaparin/warfarin. Rivaroxaban treatment was associated with a lower risk of PTS when compared to enoxaparin/warfarin; RVT however, was not a mediator in the association between PTS and type of treatment.

Topics: Adult; Anticoagulants; Brazil; Cross-Sectional Studies; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postthrombotic Syndrome; Prevalence; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Child; Humans; Pediatricians; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

In this article, we report the ultrasound aspects and recanalization rates of patients with deep venous thrombosis (DVT) in the lower limbs treated with the rivaroxaban, focusing on the recanalization rate and the ultrasonographic aspects.. This was a prospective and consecutive cohort study of patients admitted with DVT who were submitted to treatment with rivaroxaban for 6 months at the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between March 2016 and July 2018.. Fifty-one patients with DVT were admitted to the Vascular Surgery Department and received rivaroxaban for 6 months. The follow-up time was 360 days. Analyses were performed at 180 and 360 days. The rate of total venous recanalization at 360 days was 76.4% (39 patients). The incidence of partial venous recanalization was 23.5% (12 patients). At the first month, 11 patients (21.7%) continued with total occlusion of the vein, with 4 patients (6.5%) with no residual thrombi. However, at 6 months, only 2 patients (2.2%) continued with total occlusion of the vein, with 26 patients (47.8%) with no residual thrombi. At 12 months, there were 39 patients (76.4%) with no residual thrombi. Univariate and multivariate logistic regression identified the following factors related to total venous recanalization: the absence of popliteal vein reflux (odds ratio [OR], 0.386; P = 0.007), no residual thrombi (OR, 3.213; P = 0.008), femoropopliteal clot length at 1 month (OR, 3.021; P = 0.016), femoropopliteal clot length at 6 months (OR, 2.234; P = 0.008). The incidence of post-thrombotic syndrome (PTS) at 12 months was 8.3%.. In this study, patients who received oral rivaroxaban displayed satisfactory total vein recanalization rate after 6 months and 12 months. The factors associated with better total recanalization rates were the absence of popliteal vein reflux, the absence of residual thrombi in the veins, femoropopliteal clot length at 1 month (OR, 3.021; P = 0.016), and femoropopliteal clot length at 6 months (OR, 2.234; P = 0.008). Moreover, the incidence of PTS at 12 months was 8.3%.

Topics: Administration, Oral; Brazil; Factor Xa Inhibitors; Female; Humans; Incidence; Lower Extremity; Male; Middle Aged; Postthrombotic Syndrome; Predictive Value of Tests; Prospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Patency; Veins; Venous Thrombosis

Although the risk of major bleeding with non-vitamin K antagonist oral anticoagulant (NOAC) is low, life-threatening bleeding can occur.. We report a case of an 81-year-old female with deep vein thrombosis who developed bilateral spontaneous haemothorax and haemopericardium after rivaroxaban therapy. Diagnostic thoracentesis revealed a grossly bloody pleural effusion. She was treated with factor eight inhibitor bypassing agent, but the result was not satisfactory.. To our knowledge, this is the first case report of a concomitant presentation of spontaneous bilateral haemothorax and haemopericardium due to rivaroxaban use. This case highlights the potential risk of major haemorrhagic complication of NOAC, which could be life-threatening and require emergent reversal.

Topics: Aged, 80 and over; Factor Xa Inhibitors; Female; Hemothorax; Humans; Pericardial Effusion; Rivaroxaban; Venous Thrombosis

Persistent Sciatic Vein (PSV) remains a rare condition with no associated malformative syndrome or concomitant Persistent Sciatic Artery (PSA). Very few case reports have been published. We report the case of a 73-year-old man who presented to the emergency room with tenderness, edema and pain of the left calf, for up to 3 days. Biology reported an elevated d-dimer level. Doppler ultrasound diagnosed proximal left deep popliteal vein thrombosis, extended to a large vein along the sciatic nerve in the posterior compartment of the thigh, and a patent superficial femoral vein. Anticoagulation therapy was initiated immediately for at least 3 months. PSV remains an understudied condition. While its prevalence is low in the general population, this anatomical condition is associated with some specific clinical situations, such as Klippel-Trenaunay syndrome (KTS) or early varicose recurrence, especially in the posterior thigh area. To our knowledge, this is the first case report of a thrombosed PSV in a patient without a KTS.

Topics: Aged; Factor Xa Inhibitors; Humans; Male; Rivaroxaban; Thigh; Veins; Venous Thrombosis

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.

Topics: Aged; Female; Follow-Up Studies; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Registries; Rivaroxaban; Upper Extremity; Venous Thrombosis; Warfarin

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

Topics: Administration, Oral; Adult; Anticoagulants; Anticonvulsants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Male; Rivaroxaban; Stroke; Treatment Outcome; Valproic Acid; Venous Thrombosis

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

Analysed herein is the incidence rate of decompensated forms of venous insufficiency in patients who endured lower limb deep vein thrombosis and were prescribed either warfarin, rivaroxaban in therapeutic doses or rivaroxaban in a preventive dose. The study enrolled a total of 129 patients presenting with thrombotic lesions of deep veins of the lower limbs. The patients were divided into three groups depending on the anticoagulant therapy prescribed. Patients of the first and second groups for 6 months received warfarin and rivaroxaban, respectively, in therapeutic doses, and group three patients continued taking rivaroxaban in a therapeutic dose for a long time. RESULTS: Eighteen (36%) patients from the first group and two (4.5%) patients from the second group discontinued taking the anticoagulant before the scheduled date. Relapses of venous thromboembolic complications were observed in 11 (22%) group one patients and in 7 (15.9%) group two patients, with no relapses observed in the third group. Negative dynamics of the ultrasonographic picture was observed in two groups: 16% of group one patients and 9.1% of group two patients were found to develop signs of damage of previously unaltered veins or occlusion of a previously patent vein after endured thrombosis without clinical manifestation. Trophic disorders were observed in a third of patients of the first group and in one patient of the second group by the fourth year of follow up. None of the third group patients developed trophic ulcers. Statistically significant differences in the examined groups were obtained for such parameters as adherence to treatment and the degree of severity of venous insufficiency, in favour of rivaroxaban, with quality of recanalization being significantly better in the third group. A conclusion was drawn that prolonged preventive administration of new oral anticoagulants did not lead to the development of decompensated forms of venous insufficiency.. Проанализирована распространенность декомпенсированных форм венозной недостаточности у пациентов, перенесших тромбоз глубоких вен нижних конечностей, которым были назначены варфарин, ривароксабан в лечебной и ривароксабан в профилактической дозах. Всего 129 участников исследования с тромботическим поражением глубоких вен нижних конечностей были разделены на три группы с учетом назначенной антикоагулянтной терапии. Пациенты первой и второй группы в течение 6 месяцев принимали варфарин и ривароксабан, соответственно, в лечебных дозах, больные третьей группы продолжили прием ривароксабана в профилактической дозе длительно. РЕЗУЛЬТАТЫ: 18 (36%) пациентов из первой группы и 2 (4,5%) пациента из второй прекратили прием антикоагулянта ранее установленного срока. Рецидив венозных тромбоэмболических осложнений в первой группе отмечен в 11 (22%) случаях, во второй у 7 (15,9%) пациентов, в третьей рецидивов не зарегистрировано. Отрицательная динамика ультразвуковой картины отмечена в двух группах: у 16% пациентов первой группы и 9,1% больных второй группы появились признаки поражения ранее неизмененных вен или окклюзия ранее проходимой вены после перенесенного тромбоза без клинической манифестации. Трофические расстройства отмечены у трети пациентов первой группы, у одного пациента второй группы к четвертому году наблюдения; в третьей группе ни у одного пациента не развились трофические изменения. Статистически значимые различия в группах были получены по таким параметрам как приверженность к лечению и степень тяжести венозной недостаточности, в пользу ривароксабана, качество реканализации было значимо лучше в третьей группе. Сделан вывод, что длительный профилактический прием новых оральных антикоагулянтов не приводит к развитию декомпенсированных форм венозной недостаточности.

Topics: Anticoagulants; Humans; Lower Extremity; Rivaroxaban; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Thrombosis

Limited economic evaluation data for rivaroxaban compared with standard of care (SoC) exists in China. The objective of this analysis was to evaluate the cost-effectiveness of rivaroxaban compared with current SoC (enoxaparin overlapped with warfarin) for the treatment of acute deep vein thrombosis (DVT) in China.. A Markov model was adapted from a payer's perspective to evaluate the costs and quality-adjusted life years (QALYs) of patients with DVT treated with rivaroxaban or enoxaparin/warfarin. Clinical data from the EINSTEIN-DVT trial were obtained to estimate the transition probabilities. Data on Chinese health resource use, unit costs and utility parameters were collected from previously published literature and used to estimate the total costs and QALYs. The time horizon was set at 5 years and a 3-month cycle length was used in the model. A 5% discount rate was applied to the projected costs. One-way sensitivity analyses and probabilistic sensitivity analyses were undertaken to assess the impact of uncertainty on results.. Rivaroxaban therapy resulted in an increase of 0.008 QALYs and was associated with lower total costs compared with enoxaparin/warfarin (US$4744.4 vs US$5572.4, respectively), demonstrating it to be a cost-saving treatment strategy. The results were mainly sensitive to length of hospitalisation due to DVT on enoxaparin/warfarin, cost per day of hospitalisation and the difference in length of stay of rivaroxaban-treated and enoxaparin/warfarin-treated patients.. Rivaroxaban therapy resulted in a cost saving compared with enoxaparin/warfarin for the anticoagulation treatment of patients with hospitalised acute DVT in China.. NCT00440193; Post-results.

Topics: Anticoagulants; China; Cost-Benefit Analysis; Enoxaparin; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

The development of leukocytoclastic vasculitis (LCV) during apixaban therapy in a female patient being treated for deep vein thrombosis (DVT) is reported.. A 74-year-old Caucasian woman weighing 102 kg presented to a walk-in clinic with complaints of mild pain and swelling in her left leg for 2 weeks. She was diagnosed as having left lower-extremity DVT. The direct oral anticoagulant (DOAC) apixaban (10 mg twice daily for 7 days, then 5 mg twice daily for 3 months) was prescribed. At 1-week follow-up the patient stated that her DVT symptoms were slowly improving and reported that small areas of red rash had appeared bilaterally on her lower extremities. On day 23 of apixaban therapy, the patient presented to a walk-in clinic with a complaint that the rash had progressively worsened. The rash was diagnosed as LCV by dermatology consult. On day 24 of therapy, apixaban use was discontinued and the patient was initiated on rivaroxaban (20 mg daily) for the remainder of DVT treatment. LCV was found to be progressively improving on day 73, with trace petechiae. Rivaroxaban was used through the end of DVT treatment without further reports of LCV.. A female patient who developed LCV while taking apixaban for treatment of DVT was successfully transitioned to rivaroxaban therapy, leading to resolution of LCV and successful completion of DVT treatment without recurrence of LCV.

Topics: Aged; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Pyrazoles; Pyridones; Rivaroxaban; Vasculitis, Leukocytoclastic, Cutaneous; Venous Thrombosis

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

Anticoagulant treatment of pediatric central venous catheter-related venous thromboembolism (CVC-VTE) has not been specifically evaluated. In EINSTEIN-Jr, 500 children with any VTE received rivaroxaban or standard anticoagulants. A predefined analysis of the CVC-VTE cohort was performed. Children with CVC-VTE (age, birth to 17 years) were administered rivaroxaban or standard anticoagulants during the 1-month (children <2 years) or 3-month (all other children) study period. Predefined outcomes were recurrent VTE, change in thrombotic burden on repeat imaging, and bleeding. Predictors for continuation of anticoagulant therapy beyond the study period were evaluated. One hundred twenty-six children with symptomatic (n = 76, 60%) or asymptomatic (n = 50, 40%) CVC-VTE received either rivaroxaban (n = 90) or standard anticoagulants (n = 36). There was no recurrent VTE (0%; 95% confidence interval [CI], 0.0%-2.8%). Three children had the principal safety outcome: none had major bleeding and 3 children had clinically relevant nonmajor bleeding (2.4%; 95% CI, 0.7%-6.5%), all in the rivaroxaban arm. Complete or partial vein recanalization occurred in 57 (55%) and 38 (37%) of 103 evaluable children, respectively. Results were similar for symptomatic and asymptomatic CVC-VTE. Continuation of anticoagulant therapy beyond the study period occurred in 61 (48%) of children and was associated with residual VTE but only in children <2 years (odds ratio [OR], 20.9; P = .003) and continued CVC use (OR, 6.7; P = .002). Anticoagulant therapy appeared safe and efficacious and was associated with reduced clot burden in most children with symptomatic or asymptomatic CVC-VTE. Residual VTE and continued CVC use were associated with extended anticoagulation. This trial was registered at www.clinicaltrials.gov as #NCT02234843.

Topics: Anticoagulants; Child; Hemorrhage; Humans; Rivaroxaban; Thromboembolism; Venous Thrombosis

Portal vein thrombosis (PVT) is a rare presentation in dogs with protein-losing enteropathy (PLE). Rivaroxaban, an oral, selective, direct factor Xa inhibitor, has not been reported to be administrated for canine PVT and the effect is unclear in dogs with PLE.. An 11-year-old Yorkshire Terrier presented with moderate ascites. The dog had severe hypoalbuminemia (1.2 g/dL), and a portal vein thrombus was confirmed on computed tomographic angiography (CTA). On endoscopic examination, it became apparent that the hypoalbuminemia was caused by PLE, which was consequent of lymphatic dilation and lymphoplasmacytic enteritis. Therefore, the dog was initially treated with oral administrations of spironolactone and clopidogrel, with dietary fat restriction. However, a follow-up CTA showed no changes in the ascites, thrombus, and portal vein to aorta (PV/Ao) ratio. Therefore, the dog was additionally prescribed rivaroxaban and low-dose prednisolone for the portal vein thrombus and hypoalbuminemia due to lymphoplasmacytic enteritis, respectively. Following the treatment, the PV/Ao ratio decreased because of a decrease in the thrombus and the ascites disappeared completely with an elevation of albumin concentration (1.9 g/dL).. This case report demonstrated that oral administration of rivaroxaban combined with low-dose glucocorticoid was effective management for PVT in a dog with PLE.

Topics: Administration, Oral; Animals; Computed Tomography Angiography; Dog Diseases; Dogs; Factor Xa Inhibitors; Female; Glucocorticoids; Hypoalbuminemia; Portal Vein; Prednisolone; Protein-Losing Enteropathies; Rivaroxaban; 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

It's estimated that 40% to 60% of patients undergoing major orthopedic surgery of the hip or knee who do not receive thromboprophylaxis will develop deep venous thrombosis Instituto Nacional de Traumatologia e Ortopedia has established a guideline to prevent DVT with the administration of the Enoxaparin. Recently, institute stakeholders have been questioning this guideline as new oral anticoagulants that offer more comfort and efficacy, but present higher risk of bleeding, have been appearing in the market for treating deep venous thrombosis.. This study aims to validate the application of a multicriteria decision analysis in a real-world problem, the use of rivaroxaban and enoxaparin to prevent deep venous thrombosis.. The multicriteria method MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) was used in a decision conferencing process to develop an evaluation model for measuring the relative value of the drugs on each evaluation criterion, separately and globally. The model-building process was informed by a literature review and meta-analysis of randomized clinical trials with a critical appraisal of the evidence.. We report a model-structure with eight criteria, each one associated with a weighting coefficient and value function. Following a simple additive aggregation process, the model-outputs showed that Rivaroxaban was considered a robust option for DVT. Sensitivity analysis and robustness analysis were performed and testify the consistency of the results.. This article contributes to literature by showing how MACBETH method can be combined with scientific evidence and participatory group processes, for health technology assessment in hospitals.

Topics: Anticoagulants; Brazil; Enoxaparin; Hemorrhage; Humans; Orthopedic Procedures; Pharmaceutical Preparations; Postoperative Complications; Rivaroxaban; Venous Thrombosis

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

Topics: Adenosine Triphosphate; Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Factor Xa Inhibitors; Female; Hemostasis; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Rivaroxaban; Venous Thrombosis; von Willebrand Factor

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

Brain infarction is a critical complication after lung resection using video-assisted thoracoscopic surgery. Recent reports have described its association with thrombosis in the pulmonary vein (PV) stump. However, the optimal management of this complication remains controversial. We describe serial 3 cases of brain infarctions associated with thrombosis in the PV stumps, which were successfully treated with the oral Xa inhibitor rivaroxaban.. We retrospectively reviewed medical records of 3 patients. The first case was a 72-year-old man who underwent left upper lobectomy for treatment of lung adenocarcinoma. The second case was a 55-year-old man who underwent right lower segmentectomy for treatment of metastatic tumor from Barrett's esophageal carcinoma. The third case was a 73-year-old man who underwent left upper lobectomy for treatment of metastatic tumor from colon adenocarcinoma. In the first case, a large cerebellar infarction was developed and a decompressive craniotomy was performed on postoperative day 4. In the second and the third case, cerebral infarctions in the territories of right middle cerebral arteries occurred on postoperative day 2. In all cases, contrast-enhanced computed tomography demonstrated the thrombi in the stumps of the PVs. They were treated with oral administration of rivaroxaban without adverse effect, and the thrombi in the PVs disappeared within 1 month.. Blood flow stasis in the long PV stump after lung resection might contribute to thrombosis development. Oral Xa inhibitor rivaroxaban appeared to be safe and useful for the management of ischemic stroke associated with PV thrombosis after lung resection.

Topics: Administration, Oral; Aged; Brain Ischemia; Decompressive Craniectomy; Factor Xa Inhibitors; Humans; Male; Middle Aged; Pneumonectomy; Pulmonary Veins; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Venous Thrombosis

Since novel oral anticoagulants (NOACs) have been introduced in the past decade, the first option of deep vein thrombosis (DVT) treatment is toward NOACs. However, aggressive and early thrombus removal strategy is widely used for treating acute iliofemoral DVT. Consequently, optimal treatment duration, efficacy, and safety of rivaroxaban alone or in combination with catheter-directed intrathrombus thrombolysis (CDT) in acute iliofemoral DVT patients should be investigated.. Patients with recent acute iliofemoral DVT treated with combined CDT-rivaroxaban (CDT) or rivaroxaban alone (control) were followed for mean (standard deviation) of 25.7 (2.5) months. DVT evolution, treatment efficacy and safety, and predisposing factors for patency and postthrombotic syndrome (PTS) development were analyzed through duplex ultrasonography, plethysmography, venography, and computed tomographic venography.. 43.2%, 64.9%, 75.7%, and 72.2% of the CDT patients showed complete patency at 3, 6, 12, and 24 months of treatment compared with the control patients having 8.5%, 36.2%, 55.3%, and 57.4% of cumulative patency at 3, 6, 12, and 24 months, respectively (p = 0.001, 0.017, 0.088, and 0.081, respectively). The p value of the log-rank test comparing patency rates of the two groups was 0.009. The median (interquartile range, IQR) Villalta scores at 24 months were 3 (2-5) and 6 (4-8) in CDT and control patients, respectively (p = 0·001). PTS and bleeding events during therapy were, respectively, found in 35.1% and 63.8% (p = 0.017) and in 27% and 17% of CDT and control patients (p = 0.4). The Kaplan-Meier curve analysis of cumulative patency at 24 months for 6 months of rivaroxaban treatment was significant (p = 0.016).. Treatment therapy and treatment duration with rivaroxaban alone or in combination with CDT are potentially associated with vein patency at 24 months, and a 6-month lysis rate and obstructive vein can influence PTS development. A larger randomized trial is warranted to confirm these findings.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Catheterization, Peripheral; Female; Femoral Vein; Humans; Iliac Vein; Male; Middle Aged; Postthrombotic Syndrome; Rivaroxaban; Thrombolytic Therapy; Venous Thrombosis

An association between cerebral venous sinus thrombosis (CVST) and high altitude has been previously proposed, but limited published data exist to support this association. We investigated 28 cases of CVST occurring at high altitude and sought to describe patient demographics, altitude and acclimatization, hematological laboratory findings, neuroimaging, treatment, and prognosis in these cases.. Twenty-eight cases of symptomatic CVST occurring at high altitude were identified between the months of August 2017 and December 2018, in collaboration with Military Hospital, Rawalpindi and Combined Military Hospital, Skardu (Pakistan). Follow-up visits were performed at 1 and 6 months.. Twenty-seven (96%) of the patients were males, and the mean age was 33 years. In total, 32.1% were smokers. The mean NIHSS score on presentation was 5.5. 85.7% of the cases occurred at altitude higher than 8,000 feet. On average 107.8 days were spent at a high altitude prior to CVST. Totally, 71.4% had acclimatized for >2 weeks. The mean hemoglobin (Hb) value was 16.7 g/dL and 50% had d-dimer levels higher than 1,000 ng/mL. On MRI, 25% showed signs of hemorrhage and 14.3% showed infarcts. Treatments provided include low-molecular-weight heparin and Rivaroxaban and were associated with good outcomes.. CVST is not uncommon at high altitude (>8,000 feet). It is predominantly a male disease. Most patients have high Hb and high D-dimer levels. The overall outcome was good.

Topics: Acclimatization; Adult; Altitude; Anticoagulants; Biomarkers; Blood Coagulation; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Hemoglobins; Heparin, Low-Molecular-Weight; Hospitals, Military; Humans; Male; Middle Aged; Military Personnel; Pakistan; Retrospective Studies; Risk Factors; Rivaroxaban; Sinus Thrombosis, Intracranial; Time Factors; Treatment Outcome; Venous Thrombosis; Young Adult

Background Direct oral anticoagulants (DOACs) have the advantage of being administered orally at a fixed dose without laboratory monitoring, in contrast to the frequent international normalized ratio measurements used to adjust for vitamin K antagonists dosing. Rivaroxaban, has a short half-life. The anticoagulation effect rapidly decreases if medication adherence is suboptimal. Objective The purpose of this quantitative study (called RIVA) is to longitudinally describe adherence to rivaroxaban (implementation and persistence) in patients with deep vein thrombosis (DVT). Setting The community pharmacy of the Center for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland in collaboration with the angiology division of the Lausanne University Hospital (CHUV). Methods This is an observational study. Patients received rivaroxaban for 3 or 6 months: 15 mg twice a day during the first 3 weeks and then 20 mg once a day until the end of the treatment. Adherence was measured using electronic monitoring. Implementation and adherence were modelled using a generalized estimating equation model. Persistence was represented using a Kaplan-Meier survival curve. Main outcome measure Medication adherence (implementation and persistence). Results Thirty-one consecutive patients were included (68% male, mean age: 47 years old). The collected adherence data consisted of 57 inter-visit phases, 2899 electronic monitoring openings and a median follow-up of 92 days (IQR: 87; 100). Implementation to rivaroxaban was initially high [96.3 (92.8; 98.1)] but decreased during the first 3 weeks, until it reached 89.3 (76.0; 95.6). After the switch from twice a day 15 mg to a once a day 20 mg regimen, implementation increased again and remained stable [95.4 (92.2; 97.3)] for 90 days. Four patients who experienced adverse events discontinued the treatment before the end of the study and were considered non-persistent (clinically appropriate discontinuation). Conclusion Adherence to rivaroxaban in deep vein trombosis is high in persistent patients. Discontinuation is related to rivaroxaban adverse effects/toxicity. Implementation should be reinforced during the twice a day-phase, and this first 3-week experience should help patients and healthcare professionals choose the best timing for the once a day phase.

Topics: Administration, Oral; Adult; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Factor Xa Inhibitors; Female; Humans; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Rivaroxaban; Switzerland; Venous Thrombosis

to compare two anticoagulant therapy (ACT) regimens in the treatment of venous thrombosis (VT) in patients after catheter interventions - electrophysiological studies (EFIs) and ablations: enoxaparin followed by warfarin, and rivaroxaban monotherapy.. The study included patients from 18 years and older with heart rhythm disorders and planned catheter ablation. When parietal venous thrombosis (VT) were detected at the femoral vein puncture site, all patients were randomly assigned to two treatment groups. In group I enoxaparin 1 mg/kg was prescribed every 12 hours with switching to warfarin after 7 days with maintenance of the target INR values (2.0-3.0). In group II rivaroxaban therapy was started at a dose of 15 mg twise/day for 21 days with a further transition to a dose of 20 mg/day. The total period of observation and treatment of patients was at least 3 months.. 408 patients were observed, 42 (10.3%) patients with parietal VT were divided into two treatment groups. In group I (n=16) complete lysis of VT was noted by the 7th day of treatment in 7 (58.3%) patients, however this scheme was associated with a greater risk of complications (р=0.003) at the puncture site in the form of arteriovenous fistulae (n=1; 8.3%) and intermuscular hematomas (n=4; 25%). In group II (n=26), no complications were noted, the lysis time of VT was on average 21 days (n=18; 69.2%). Complete lysis of VT was noted in both groups at the time of the control observation point (3rd month).. The efficiency of the two VT treatment regimens was comparable. Enoxaparin therapy is associated with a high risk of local complications, namely intermuscular hematomas (n=4; 25%) and arteriovenous fistulas (n=1; 8.3%). Rivaroxaban monotherapy is safer (p=0.003); in Group II none of the patients had any complications.. Цель исследования: сравнить две схемы антикоагулянтной терапии (АКТ) в лечении венозных тромбозов (ВТ) у пациентов после внутрисердечных катетерных вмешательств - электрофизиологических исследований (ЭФИ) и абляций: эноксапарина с последующим назначением варфарина и монотерапии ривароксабаном. Материалы и методы. В исследование включали пациентов от 18 лет с нарушениями ритма сердца и планируемыми катетерными вмешательствами. При выявлении пристеночного ВТ в месте пункции бедренной вены пациентов рандомизировали на две группы лечения: в группе I проводилась АКТ эноксапарином 1 мг/кг каждые 12 ч с переходом на варфарин через 7 дней с поддержанием целевых значений международного нормализованного отношения (2,0-3,0), в группе II - АКТ ривароксабаном 15 мг 2 раза/сут в течение 21 дня с дальнейшим переходом на дозу 20 мг/сут. Срок наблюдения и лечения пациентов составил 3 мес. Результаты. Наблюдали 408 пациентов, из них 42 (10,3%) пациента с пристеночным ВТ распределили на две группы лечения. В группе I (n=16) у 7 (58,3 %) больных отмечен полный лизис ВТ к 7-му дню лечения, однако эта схема сопряжена с большим риском осложнений (р=0,003) со стороны места пункции в виде артериовенозных соустий (n=1; 6,25%), межмышечных гематом (n=4; 25%). В группе II (n=26) осложнений не отмечалось, время лизиса ВТ в среднем составило 21 день (n=18; 69,2%). В обеих группах на момент проведения контрольной точки наблюдения (3-й месяц) отмечен полный лизис ВТ. Заключение. Эффективность двух схем лечения ВТ оказалась сопоставимой. Терапия эноксапарином сопряжена с большим риском развития местных осложнений: межмышечных гематом (n=4; 25%), артериовенозных соустий (n=1; 8,3%). Монотерапия ривароксабаном была более безопасна (р=0,003), в группе II осложнений не отмечено.

Topics: Anticoagulants; Cardiac Catheters; Enoxaparin; Humans; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

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

The study was initiated following the observation of complete recanalization of thrombus in subjects with DVT treated with rivaroxaban after 1-2 weeks. The aim of this observational retrospective study was to evaluate clinically and by means of echo color Duplex, the fibrinolytic effect of rivaroxaban in patients with recent and previous DVT. To accomplish this two populations of patients were evaluated.. Group 1 was comprised of 31 patients (ranging in age 52-73 years) with popliteal-femoral DVT (12 months ago) treated with standard anticoagulant therapy. In these patients, we found a complete superficial femoral recanalization and partial recanalization of the popliteal vein (30% of residual thrombus). The patients had normal creatinine clearance and liver function. The patients were switched from warfarin to rivaroxaban due to a lack of compliance with warfarin therapy. Group 2 was comprised of 22 patients (ranging in age 65-82 years) with previous popliteal-femoral DVT and documented complete common femoral veins recanalization who presented with a recent superficial femoral vein re-thrombosis (1 week before). The patients had normal creatinine clearance and liver function. The patients switched from warfarin to rivaroxaban due to a lack of compliance with warfarin therapy.. In group 1, all patients exhibited the complete recanalization of the popliteal veins after 4 weeks of rivaroxaban therapy. In group 2, all patients exhibited the complete recanalization of the popliteal veins after 4 weeks, and the complete recanalization of the acute re-thrombosis of the superficial femoral veins after 2 weeks of rivaroxaban therapy. No adverse events for both groups were observed.. Our results suggest that rivaroxaban could have a pro-fibrinolytic effect not only on recent thrombus but also on organized thrombus that results in a complete recanalization of affected veins. It is proposed that this lytic effect will preserve venous valve structure and lead to a reduction of incidence of post-thrombotic syndrome in rivaroxaban treated patients.

Topics: Aged; Aged, 80 and over; Factor Xa Inhibitors; Female; Femoral Vein; Humans; Male; Middle Aged; Popliteal Vein; Postthrombotic Syndrome; Rivaroxaban; Thrombolytic Therapy; Treatment Outcome; Ultrasonography, Doppler, Duplex; Venous Thrombosis

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Brain; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thrombosis

Whilst athletes are the epitome of health, venous thromboembolisms (VTE) including deep vein thrombosis and pulmonary embolism have been demonstrated to occur in well-trained athletes. VTE is frequently misdiagnosed and poorly treated within this population, often resulting in career or life-threatening ramifications. Furthermore, VTE risk rises with increasing age (> 40 years), potentially affecting masters athletes. A 44-year-old well-trained male cyclist volunteered to participate in a research project investigating the influence of exercise on haemostasis in well-trained athletes. The cyclist presented with elevated D-Dimer levels both pre- (2251 ng/mL) and post-exercise (2653 ng/mL). The cyclist reported constant mild-pain in the left mid-calf region, with a cold tingling sensation in their left foot. Diagnosis of DVT was confirmed via a DVT squeeze test and Doppler ultrasound, with the clot located in the left popliteal vein. During the research project, the cyclist was exposed to numerous thrombogenic risk factors including travel, dehydration, prolonged sitting and exercise. The DVT in the popliteal vein may have resulted from repetitive movements associated with cycling. Additionally, hypertrophy of the gastrocnemius muscle may have impinged the vein. When diagnosing DVT within a cycling population, PVES should not be overlooked as a contributing factor.

Topics: Adult; Bicycling; Factor Xa Inhibitors; Humans; Male; Muscle Contraction; Peripheral Vascular Diseases; Physical Endurance; Popliteal Vein; Risk Factors; Rivaroxaban; Syndrome; Treatment Outcome; Ultrasonography, Doppler; Venous Thrombosis

Topics: Humans; Pyrazoles; Pyridones; Rivaroxaban; Venous Thrombosis

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

Renown Health (Reno, Nevada), a large, locally owned, not-for-profit integrated health care network, has developed an institution-wide policy to shift the treatment of deep vein thrombosis (DVT) from a short-acting anticoagulant and vitamin K antagonist to the direct oral anticoagulant rivaroxaban combined with pharmacy-directed follow-up at an outpatient anticoagulation clinic. We examined data on hospitalizations and costs pre-/post-policy change.. Data were obtained from the electronic health records of adults with newly diagnosed DVT treated at Renown Health. A quasi-experimental design was used to evaluate patients who received a DVT diagnosis before versus after the policy change. Primary outcomes were number of all-cause inpatient nights at 30 and 60 days post-DVT index date. Secondary outcomes were costs of all-cause overnight stays at 30 and 60 days post-DVT index. Outcomes were evaluated in propensity-weighted logistic regression and generalized linear models.. There were 343 patients pre-policy change and 266 post-policy change. In the first 30 days postindex, the mean (95% CI) numbers of propensity-weighted all-cause inpatient nights were 1.27 (0.83-1.95) prechange and 0.66 (0.42-1.02) postchange (P = 0.038). Mean propensity-weighted estimated all-cause hospital costs in patients diagnosed as outpatients were $7848 ($4990-$12,344) prechange and $2466 ($1553-$3915) postchange (P <0.001). Mean costs of all-cause overnight stays in inpatient-diagnosed DVT patients were $8907 prechange and $7449 postchange (P = 0.600). In the first 60 days postindex, the mean number of all-cause inpatient nights (P = 0.219) and mean costs of all-cause overnight stays (P = 0.275) were not significantly different before and after the policy change.. Changing institutional policy to increase the utilization of a direct oral anticoagulant and pharmacist-led outpatient anticoagulation clinics may reduce length of hospital stay and decrease health care expenditures in the treatment of DVT.

Topics: Adult; Aged; Anticoagulants; Female; Health Care Costs; Hospitalization; Humans; Inpatients; Male; Middle Aged; Organizational Policy; Outpatients; Rivaroxaban; Venous Thrombosis; Warfarin

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

Many strategies for venous thromboembolism (VTE) prophylaxis following hip and knee arthroplasty exist, with extensive controversy regarding the optimum strategy to minimize risk of VTE and bleeding complications. Data from the American Board of Orthopedic Surgery Part II (oral) Examination case list database was analyzed to determine efficacy, complication rates, and prescribing patterns for different prophylactic strategies.. The American Board of Orthopedic Surgery case database was queried utilizing Current Procedural Terminology codes 27447 and 27130 for primary total knee and hip arthroplasty, respectively. Geographic region, patient age, gender, deep vein thrombosis prophylaxis strategy, and complications were obtained. Less aggressive prophylaxis patterns were considered if only aspirin and/or sequential compression devises were utilized. More aggressive VTE prophylaxis patterns were considered if any of low-molecular-weight heparin (enoxaparin), warfarin, rivaroxaban, fondaparinux, or other strategies was used.. In total, 22,072 cases of primary joint arthroplasty were analyzed from 2014 to 2016. The national rate of less aggressive VTE prophylaxis strategies was 45.4%, while more aggressive strategies were used in 54.6% of patients. Significant regional differences in prophylactic strategy patterns exist between the 6 regions. The predominant less aggressive prophylaxis pattern was aspirin with sequential compression devises at 84.8% with 14.8% receiving aspirin alone. Use of less aggressive prophylaxis strategy was significantly associated with patients having no complications (95.5% vs 93.0%). Use of more aggressive prophylaxis patterns was associated with higher likelihood of mild thrombotic (0.9% vs 0.2%), mild bleeding (1.3% vs 0.4%), moderate thrombotic (1.2% vs 0.4%), moderate bleeding (2.7% vs 2.1%), severe thrombotic (0.1% vs 0.0%), severe bleeding events (1.2% vs 0.9%), infections (1.9% vs 1.3%), and death within 90 days (0.7% vs 0.3%). Similar results were found in subgroup analysis of total hip and knee arthroplasty patients.. It was not possible to ascertain the individual rationale for use of more aggressive VTE prophylaxis strategies; however, more aggressive strategies were associated with higher rates of bleeding and thrombotic complications. Less aggressive strategies were not associated with a higher rate of thrombosis.. Therapeutic Level III.. All views expressed in the study are the sole views of the authors and do not represent the views of the American Board of Orthopedic Surgery.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Databases, Factual; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Orthopedic Procedures; Orthopedics; Practice Patterns, Physicians'; Risk Factors; Rivaroxaban; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Aged; Computed Tomography Angiography; Factor Xa Inhibitors; Humans; Male; Phlebography; Prosthesis Implantation; Rivaroxaban; Treatment Outcome; Vascular Patency; Vena Cava Filters; Vena Cava, Inferior; Venous Thrombosis

Topics: Adult; Aged; Endothelial Cells; Factor Xa Inhibitors; Fibrinolysis; Humans; Middle Aged; Plasminogen Activator Inhibitor 1; Rivaroxaban; Venous Thrombosis

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

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

Hypercoagulability can lead to thromboembolic events that are a life-threatening complication of nephrotic syndrome (NS). Conventional anticoagulants are first-line treatment in the presence of demonstrated thrombosis in NS. Direct-acting oral anticoagulants (DOACs) have provided useful alternatives for the prevention and treatment of thromboembolic events.. A 59-year-old male developed lower limbs deep vein thrombosis (DVT) during the early course of NS but presented poor response to oral therapeutic doses of rivaroxaban. The decision was made to switch from rivaroxaban to heparin and subsequently bridged to warfarin. The patient presented significant clinical symptom improvement.. NS with Lower limbs DVT.. Rivaroxaban was discontinued and switch to heparin and subsequently bridged to warfarin.. Venography result of both lower limb vein showed the venous wall was smooth without obvious stenosis or obstruction. Edema of the patient's lower limbs gradually improved and disappeared.. The existing published data on the application of DOACs in NS are limited. DOACs have an immediate anticoagulant effect and have demonstrated safety and efficacy and required no routine monitoring, however, application of these agents in NS likely requires further investigation before widespread adoption.

Topics: Anticoagulants; Humans; Male; Middle Aged; Nephrotic Syndrome; Rivaroxaban; Thrombophilia; Venous Thrombosis; Warfarin

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

Factor Xa (fXa) is a crucial player in various thromboembolic disorders. Inhibition of fXa can provide safe and effective antithrombotic effects. In this study, a series of anthranilamide compounds were designed by utilizing structure-based design strategies. Optimization at P1 and P4 groups led to the discovery of compound 16g: a highly potent, selective fXa inhibitor with pronounced in vitro anticoagulant activity. Moreover, 16g also displayed excellent in vivo antithrombotic activity in the rat venous thrombosis (VT) and arteriovenous shunt (AV-SHUNT) models. The bleeding risk evaluation showed that 16g had a safer profile than that of betrixaban at 1 mg/kg and 5 mg/kg dose. Additionally, 16g also exhibited satisfactory PK profiles. Eventually, 16g was selected to investigate its effect on hypoxia-reoxygenation- induced H9C2 cell viability. MTT results showed that H9C2 cell viability can be remarkably alleviated by 16g.

Topics: Animals; Anticoagulants; Arteriovenous Shunt, Surgical; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Factor Xa; Molecular Docking Simulation; Molecular Structure; ortho-Aminobenzoates; Rats; Structure-Activity Relationship; Venous Thrombosis

Topics: Factor Xa Inhibitors; Humans; Rivaroxaban; Treatment Outcome; Venous Thrombosis

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

Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome involved in the metabolism of nearly 50% of all medications. Thus, its effective concentration depends on multiple pharmacologic parameters.. The primary goal of our research was to study the correlation between the CYP3A family activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83 years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days after diagnosis and 20 mg/day for the follow-up period of 6 months. During the study period, Doppler ultrasound was performed weekly to assess the clot dynamics and recanalization time.. We found a direct statistically reliable correlation between CYP3A4 activity and both peak and trough rivaroxaban levels. A correlation was also found between the initial clot length and the time to full recanalization r = 0.764 (0.554-0.883), p < 0.0001. No significant link was found between either the glomerular filtration rate and peak rivaroxaban concentrations or between CYP3A4 activity and the treatment effectiveness parameters. No connection between renal function and rivaroxaban concentration was established in our study, which agrees with the clinical trials data that allow unlimited rivaroxaban use in patients with glomerular filtration rate >30 mL/min.. The direct link between the initial clot length and time to full recanalization that has been found means that patients with more advanced stages of thrombosis need more time to reach recanalization than their counterparts with a less severe condition.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cytochrome P-450 CYP3A; Female; Humans; Male; Middle Aged; Rivaroxaban; Russia; Venous Thrombosis

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

The non-vitamin K antagonist oral anticoagulant rivaroxaban is indicated in prevention and treatment of venous thromboembolism (VTE). A 60-year-old male patient complained of bilateral ptosis after administration of rivaroxaban for deep vein thrombosis (DVT). Myasthenia gravis (MG) was confirmed by positive serum antiacetylcholine receptor antibody test. No mediastinal thymoma was found. The ocular myasthenia reversed after discontinuing rivaroxaban treatment. Nevertheless, ptosis recurred and chronic oral pyridostigmine bromide treatment was necessary. The mechanism of MG development by rivaroxaban therapy is not completely understood. The development of rivaroxaban-induced autoimmune disease could be based on cross-reactivity between antibodies against rivaroxaban-derived antigens or by T-cell activation. To our knowledge, this report of ocular myasthenia by rivaroxaban administration is the first in the literature. Despite the benefits of rivaroxaban, it is important to recognize unexpected immune-related adverse events.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Autoantibodies; Biomarkers; Blepharoptosis; Cholinesterase Inhibitors; Drug Substitution; Factor Xa Inhibitors; Humans; Male; Middle Aged; Myasthenia Gravis; Oculomotor Muscles; Pyridostigmine Bromide; Receptors, Cholinergic; Rivaroxaban; Treatment Outcome; Venous Thrombosis

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

Vascular manifestations including pulmonary artery aneurysms and venous thrombosis are seen in up to 14% of patients with Behcet's disease. We report a patient who had recurrent deep vein thrombosis (DVT) as the presenting symptom of Behcet's Disease.. A 19-year-old male who presented with acute iliofemoral DVT, confirmed by intravascular ultrasound (IVUS) and venogram. May-Thurner syndrome was also observed. Repeated catheter-based pharmacomechanical thrombolysis, thrombectomy, and subsequent iliac vein stenting were performed. The patient was then discharged on rivaroxaban and aspirin.. Five months later, the patient experienced left calf pain. In the interim, he had been diagnosed with Behcet's disease by a rheumatologist who was consulted due to oral ulcers and skin lesions and accordingly started on prednisone, colchicine, and azathioprine. At this time, IVUS and venogram revealed thrombotic occlusion of the previously placed stent. Tissue plasminogen activator was infused into the stent, and pharmacomechanical thrombectomy restored flow through the left iliac veins. Follow-up laboratory workup revealed that subtherapeutic azathioprine dosing, and after appropriate adjustment, the patient has been asymptomatic for 12 months.. Acute refractory DVT is a possible presenting symptom of Behcet's disease, which may be complicated by May-Thurner syndrome. Such patients should receive therapeutic immunosuppression in addition to anticoagulation.

Topics: Aspirin; Behcet Syndrome; Endovascular Procedures; Factor Xa Inhibitors; Femoral Vein; Humans; Iliac Vein; Immunosuppressive Agents; Male; May-Thurner Syndrome; Mechanical Thrombolysis; Phlebography; Platelet Aggregation Inhibitors; Recurrence; Rivaroxaban; Stents; Thrombectomy; Treatment Outcome; Ultrasonography, Interventional; Venous Thrombosis; Young Adult

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

Objective This study was performed to evaluate the efficacy of rivaroxaban versus nadroparin for preventing deep venous thrombosis (DVT) in elderly patients with osteoporosis undergoing initial total hip arthroplasty (THA) for femoral neck fractures. Methods Prospectively maintained databases were reviewed to retrospectively compare elderly patients with osteoporosis who underwent initial THA for femoral neck fractures from 2007 to 2015. The patients received peroral rivaroxaban at 10 mg/day for 2 weeks or subcutaneous injections of nadroparin at 0.3 mL/day for 2 weeks until the primary analysis cut-off date. The time to first on-study DVT was the primary endpoint. Results In total, 399 patients were included (rivaroxaban group: n=200; mean age, 70.20 ± 9.16 years and nadroparin group: n = 199; mean age, 69.90 ± 8.87 years), with a mean 3-year follow-up. The time to first on-study DVT was significantly longer in the rivaroxaban than nadroparin group (12 and 5 days, respectively). The incidence of DVT within the 2-week follow-up was significantly higher in the nadroparin than rivaroxaban group (6.8% and 19.7%, respectively), but this difference was no longer present at the final follow-up. Conclusion Rivaroxaban was associated with a significant reduction in the occurrence of first on-study DVT compared with nadroparin.

Topics: Aged; Arthroplasty, Replacement, Hip; Blood Coagulation; Demography; Female; Femoral Neck Fractures; Humans; Male; Nadroparin; Osteoporosis; Retrospective Studies; Risk Factors; Rivaroxaban; Venous Thrombosis

Acute mesenteric venous thrombosis (MVT) is the rarest cause of acute mesenteric ischaemia, so thrombosis of a variant inferior mesenteric vein (IMV) is especially uncommon in the setting of antiphospholipid syndrome (APS). Here, we present such a case of seronegative APS initially manifesting as an anomalous IMV thrombosis in a 76-year-old woman. Although guidelines support anticoagulation with vitamin K antagonists in these patients, we anticoagulated with rivaroxaban (a direct oral anticoagulant (DOAC)) due to patient preference, which resulted in complete clinical and endoscopic resolution. IMV thrombosis is a rare form of MVT, only two case reports describe successful anticoagulation with DOACs in the setting of MVT and none report APS as an underlying aetiology. Therefore, this case provides the opportunity to review the pathophysiology of MVT, APS and their medical management including current trends in anticoagulation.

Topics: Acute Disease; Aged; Antiphospholipid Syndrome; Diagnosis, Differential; Factor Xa Inhibitors; Female; Humans; Mesenteric Veins; Rivaroxaban; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis

Topics: Aged; Factor Xa Inhibitors; Female; Headache; Hormone Replacement Therapy; Humans; Jugular Veins; Neck Pain; Pacemaker, Artificial; Phlebography; Rivaroxaban; Tomography, X-Ray Computed; Ultrasonography, Doppler; Venous Thrombosis

Congenital disorders of glycosylation (CDG) are rare inborn diseases of glycan component of N-glycosylated proteins. We report here the case of a 28-year-old patient with CDG syndrome type Ia, who presented with a deep venous thrombosis in the left suro-popliteal vein with no known triggers or antecedents. The patient was treated with rivaroxaban for six months. Blood tests performed after discontinuing anticoagulant treatment showed multiple abnormalities affecting the proteins involved in haemostasis (both coagulation factors and inhibitors), i.e. a combined factor XI, antithrombin and protein C deficiency (35%, 41%, and 42% respectively) associated with a moderate increase of FVIII (179%) and VWFAg (163%) without inflammation. Patient results are here discussed with regard to the limited number of articles addressing haemostasis in this rare disease, as the occurrence of deep venous thrombosis remains uncommon in the literature.

Topics: Adult; Congenital Disorders of Glycosylation; Female; Humans; Phosphotransferases (Phosphomutases); Rare Diseases; Rivaroxaban; Treatment Outcome; Venous Thrombosis

A 77-year-old woman presented to the hospital with symptoms of progressive shortness of breath with associated right-sided pleuritic pain. The patient had begun noting dyspnea on exertion, limiting her ability to go on hikes over the few days prior to admission. Her medical history is significant for carcinoid tumor status postresection in 2012 without recurrence. She has no history of thromboembolism or clotting disorders, and she has no history of smoking or drug abuse. Current medications include amlodipine, celecoxib, hydrochlorothiazide, and rosuvastatin.

Topics: Acute Disease; Aged; Chest Pain; Dyspnea; Echocardiography; Factor Xa Inhibitors; Female; Humans; Pulmonary Veno-Occlusive Disease; Rivaroxaban; Tomography, X-Ray Computed; Venous Thrombosis

Topics: Aged, 80 and over; Demyelinating Diseases; Factor Xa Inhibitors; Humans; Male; Polyneuropathies; Rivaroxaban; Venous Thrombosis

A 16-year-old boy presented to hospital with a 6-day history of diarrhoea, vomiting and abdominal pain. During his admission he was found to be hypotensive, tachycardic and persistently feverish. Blood cultures taken on admission isolated

Topics: Abdominal Pain; Adolescent; Anti-Bacterial Agents; Drainage; Factor Xa Inhibitors; Fusobacterium necrophorum; Humans; Jugular Veins; Lemierre Syndrome; Magnetic Resonance Imaging; Male; Pharyngitis; Pleural Effusion; Rivaroxaban; Shock, Septic; Venous Thrombosis

Inferior vena cava (IVC) thrombosis is very rare, particularly in the absence of an apparent congenital caval abnormality or hypercoagulable state. We herein report an unusual case of a healthy and active 62-year-old male bodybuilder with a mass-like IVC thrombus. We placed an IVC filter and began treatment with rivaroxaban. The patient recovered successfully, and the IVC thrombus completely disappeared three months later. This case suggested that extrinsic compression of IVC by a tightened weightlifting belt around the abdomen is a triggering factor of IVC thrombosis, and rivaroxaban, a new oral anticoagulant, may be a useful option for treatment.

Topics: Anticoagulants; Humans; Male; Middle Aged; Rivaroxaban; Vena Cava, Inferior; Venous Thrombosis

Iatrogenic iliac vein dissection secondary to femoral artery puncture is a rare complication that has not yet been documented. A 55-year-old woman presented to our institution with acute right iliofemoral thrombosis 2 weeks after transfemoral cerebral angiography. She was previously healthy and was not taking any medication. Right iliofemoral vein dissection was diagnosed by computed tomography angiography and confirmed by conventional venography. The patient was treated endovascularly with stent insertion, and the venous outflow was patent on the 6-month follow-up computed tomography angiogram.

Topics: Catheterization, Peripheral; Computed Tomography Angiography; Endovascular Procedures; Factor Xa Inhibitors; Female; Femoral Artery; Femoral Vein; Humans; Iatrogenic Disease; Iliac Vein; Middle Aged; Phlebography; Punctures; Regional Blood Flow; Rivaroxaban; Stents; Treatment Outcome; Vascular Patency; Vascular System Injuries; Venous Thrombosis

Deep venous thrombosis is one of the common complications after major surgery in the Department of Orthopedics. The selective knee replacement of the lower extremities is more likely to cause the occurrence of DVT. The most commonly used anticoagulants in the Department of Orthopedics now include low molecular weight heparin (LMWH), Rivaroxaban, ordinary heparin, aspirin and warfarin. At present, the clinical application of low molecular weight heparin is the most, and the effect is the most accurate. This study compared the efficacy and safety of three commonly used anticoagulants such as aspirin, LMWH and Rivaroxaban in preventing VTE after hip and knee arthroplasty, so as to provide a theoretical basis for selecting suitable anticoagulant drugs in clinic. It has been proved that LMWH has good efficacy and safety in the prevention of VTE after hip and knee arthroplasty and is a priority anticoagulant. Rivaroxaban can effectively control the occurrence of DVT and the drug is convenient, but it will increase the risk of bleeding and should be used carefully.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Rivaroxaban; Venous Thrombosis

Topics: Adult; Female; Humans; Liver Failure; Rivaroxaban; Venous Thrombosis

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

Venous thromboembolism (VTE) is a serious complication following total joint replacement. The use of rivaroxaban, a highly selective and direct factor Xa inhibitor, has been used widely as a safe and efficacious way to prevent VTE after total joint replacements. However, little is known about the diagnostic efficacy of plasma D-dimer test on deep vein thrombosis (DVT) in patients using rivaroxaban for thromboprophylaxis. The study is aimed to investigate the trend and the diagnostic efficacy of D-dimer test on DVT in patients with primary total knee arthroplasty (TKA) using rivaroxaban for thromboprophylaxis.. Two hundred TKA patients using rivaroxaban postoperatively as chemical prophylaxis were reviewed. D-dimer levels were checked at 4 h after the surgery and on postoperative days 1 and 4. Venography was used to document the presence of DVT. The Mann-Whitney U test was used to detect the differences in the D-dimer levels at different time points in patients with and without DVT, followed by Bonferroni corrections for p values. Receiver operating characteristics (ROC) curves were constructed to determine the best cutoff values of the D-dimer test at each time point after the surgery.. Twenty-nine of the 200 patients were found to have deep vein thrombosis by venography, resulting in an incidence of 14.5%. All patients with DVTs occurred in the distal calf veins, and only one patient was symptomatic. We found significant differences in D-dimer concentration between patients with and without DVT at postoperative day 4. The best cutoff value determined by receiver operating characteristics analysis was 3.8 mg/L at postoperative day 4, with an AUC equal to 63.5%, and a sensitivity, specificity, PPV, and NPV of 58.6, 76, 29.3, and 91.5%, respectively.. Rivaroxaban was effective on reducing DVT in patients undergoing TKA. Because all the DVTs occurred in the leg veins, decreased thrombus volume and size might result in poor accuracy of plasma D-dimer test in prediction or diagnosis of postoperative DVT.

Topics: Aged; Arthroplasty, Replacement, Knee; Chemoprevention; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Rivaroxaban; Venous Thrombosis

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

Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are at high risk of deep vein thrombosis (DVT) postoperatively, necessitating the use of prophylaxis medications. This investigation used a large claims database to evaluate trends in postoperative DVT prophylaxis and rates of DVT within 6 months after THA or TKA.. Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases were reviewed from 2004 to 2013 for patients who underwent THA or TKA. Data were collected on patient age, sex, Charlson Comorbidity Index, and hypercoagulability diagnoses. Postoperative medication claims were reviewed for prescribed aspirin, warfarin, enoxaparin, fondaparinux, rivaroxaban, and dabigatran.. A total of 369,483 patients were included in the analysis, of which 239,949 patients had prescription medication claims. Warfarin was the most commonly prescribed anticoagulant. Patients with a hypercoagulable diagnosis had markedly more DVTs within 6 months after THA or TKA. More patients with a hypercoagulable diagnosis were treated with warfarin or lovenox than other types of anticoagulants. A multivariate regression analysis was performed, showing that patients prescribed aspirin, fondaparinux, and rivaroxaban were markedly less likely than those prescribed warfarin or enoxaparin to have a DVT within 6 months after THA or TKA.. After THA and TKA, warfarin is the most commonly prescribed prophylaxis. Patients with hypercoagulability diagnoses are at a higher risk of postoperative DVT. The likelihood of DVT within 6 months of THA and TKA was markedly higher in patients treated with warfarin and lovenox and markedly lower in those treated with aspirin, fondaparinux, and rivaroxaban.. Level III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Clinical Decision-Making; Dabigatran; Databases, Factual; Enoxaparin; Female; Fondaparinux; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

Osteoarthritis (OA) is the third most common diagnosis made by general practitioners in older patients. The purpose of the current study is to investigate effects rivaroxaban had on both hidden blood loss and blood transfusion rate (BTR) in patients with knee OA (KOA) after going through a total knee replacement (TKR).Between the time periods of December 2011 up until January 2015, a total of 235 patients underwent TKR and were selected to be assigned to either the rivaroxaban or nonanticoagulant groups. Coagulation function indexes before surgery and following administration of rivaroxaban, total blood loss, hidden blood loss, dominant blood loss, blood transfusion volume, hemoglobin reduction, degree of postoperative pain (visual analogue scale), the degree of knee swelling, and range of motion following surgery were all recorded. Hospital for special surgery (HSS) scores offered an objective evaluation for the knee joint functions before surgery at the intervals of 2 weeks and after surgery at intervals of 3 months, 6 months, 12 months, and 24 months.Patients in the rivaroxaban group had shown a higher hidden blood loss, as well as a higher BTR, compared to those involved in the nonanticoagulant group. BTR was found to have been 49.59% in the rivaroxaban group, and 35.09% for the nonanticoagulant group. Patients in the rivaroxaban group had lower degrees of knee swelling than those involved in the nonanticoagulant group. There was no deep vein thrombosis (DVT) detected in the rivaroxaban group, whereas 5 DVT cases were detected in the nonanticoagulant group. In the rivaroxaban group, the HSS scores of the knee joint functions were remarkably higher at the 2-week mark in succession to the surgery than those involved with the nonanticoagulant group.This overall data demonstrated that KOA patients after TKR had presented with a higher hidden blood loss, BRT, and lower swelling degrees of the knee joint after being treated by the rivaroxaban.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Edema; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain, Postoperative; Range of Motion, Articular; Rivaroxaban; Venous Thrombosis

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

Newer oral anticoagulants like rivaroxaban are increasingly becoming the mainstay of treatment in systemic thrombosis. However cerebral venous thrombosis (CVT) is conventionally treated with heparin followed by oral vitamin K antagonists. Currently very little information is available about the use of rivaroxaban in CVT. Rivaroxaban has been used only after the initial treatment with heparin in the available studies.. All patients with CVT between January 2017 and June 2017 were initiated directly on oral rivaroxaban. Critically ill patients including those requiring surgical intervention were excluded. The modified Rankin scale was used to assess clinical severity and a scale of 0-1 was defined as excellent outcome. Recanalization was assessed at 3 months follow-up with MR angiography. Complications of the drug including bleeding episodes during treatment and at follow-up were noted.. Twenty patients were initiated on rivaroxaban and followed up for a mean duration of 6 months. Eighty percent (16/20) were males and the mean age was 34.1 years. Associated cerebral hemorrhagic infarcts were seen in 11(55%).Outcome was excellent in 19(95%). Complete recanalization was noted in 12(60%) and partial recanalization in 8(40%). No complications emerged out of the drug use.. In clinically stable CVT rivaroxaban is safe and effective and may be used without previous heparin therapy. This can shorten the duration of hospitalization thereby decreasing the costs of treatment.

Topics: Administration, Oral; Adolescent; Adult; Aged; Factor Xa Inhibitors; Female; Follow-Up Studies; Heparin; Humans; Intracranial Thrombosis; Male; Middle Aged; Prospective Studies; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Young Adult

Topics: Anticoagulants; Antithrombins; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Perioperative Care; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Background Standard treatment for deep venous thromboembolism involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for venous thromboembolism and does not require routine coagulation monitoring. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (tinzaparin/warfarin). Methods A total of 184 patients who were under anticoagulant therapy with warfarin or rivaroxaban for extended deep venous thromboembolism were retrospectively evaluated; 59 received rivaroxaban and 125 received warfarin therapy. Assessments were made on age, gender, place of residence, the duration of anticoagulation, mean international normalized ratio value, the effective rate of international normalized ratio (time in the therapeutic range), bleeding-related complication rate, duration of hospitalization due to complications, the number of annual outpatient department admission, cost for drug, cost for hospitalization, cost for outpatient department admission and international normalized ratio measurements. Results The annual outpatient cost is higher in warfarin group (147.09 ± 78 vs. 62.32 ± 19.79 USD p < 0.001). But annual drug cost is higher in rivaroxaban group (362.6 vs. 71.55 ± 31.01 USD p < 0.001). Overall cost of rivaroxaban group is higher than warfarin group (476.25 ± 36.78 vs. 364.82 ± 174.44 USD). Warfarin is not cost-effective when non-drug costs (342.5 ± 174.44 vs. 113.65 ± 36.77) and hospital costs (173.85 ± 122.73 vs. 64.9 ± 23.55 USD) were analyzed. Conclusion This analysis suggests that rivaroxaban has lower costs than warfarin in terms of outpatient department admission and hospital costs due to complications; however, warfarin was more economic when all cost parameters were considered. Time in the therapeutic range was found as 56% for warfarin that should be taken into account while analyzing costs and benefits.

Topics: Adult; Aged; Ambulatory Care; Anticoagulants; Blood Coagulation; Cost Savings; Cost-Benefit Analysis; Drug Costs; Drug Monitoring; Factor Xa Inhibitors; Female; Health Care Costs; Hemorrhage; Hospital Costs; Humans; International Normalized Ratio; Male; Middle Aged; Models, Economic; Retrospective Studies; Risk Factors; Rivaroxaban; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Ankle Injuries; Deprescriptions; Estradiol; Estrogen Replacement Therapy; Estrogens; Factor Xa Inhibitors; Female; Health Services for Transgender Persons; Humans; Immobilization; Male; Progesterone; Progestins; Rivaroxaban; Sprains and Strains; Transdermal Patch; Transgender Persons; Travel; Venous Thrombosis

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

The present study estimates the effect of rivaroxaban on preventing deep vein thrombosis (DVT) in aged diabetics with femoral neck fractures after hip replacement. Our study consisted of 236 aged diabetics with femoral neck fractures, which were divided into the rivaroxaban and control groups. Reaction time (R time), clot formation time (K time), α angle (α), maximum amplitude (MA), clot elasticity (G) and coagulation index (CI), prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. DVT was diagnosed by color duplex Doppler ultrasound (CDDU). The risk factors of DVT were analysed by logistic regression analysis. Compared with the control group, in the rivaroxaban group, R time and K time were extended and α, MA and G decreased 1 day before operation. One day after operation, the rivaroxaban group had less PT and APPT and lower incidence of DVT than the control group. In the two groups, preoperative and postoperative PT and APPT significantly differed. Body mass index (BMI) ≥25, abnormal coagulation indicators, use of cemented femoral hip prosthesis, high haemoglobin content and non-ankle pump exercise after operation were the risk factors for DVT. Rivaroxaban could prevent DVT in aged diabetics with femoral neck fractures after hip replacement.

Topics: Aged; Arthroplasty, Replacement, Hip; Blood Coagulation; Body Mass Index; Diabetic Angiopathies; Female; Femoral Neck Fractures; Humans; Logistic Models; Male; Partial Thromboplastin Time; Postoperative Complications; Postoperative Period; Preoperative Period; Prothrombin Time; Reaction Time; Risk Factors; Rivaroxaban; Venous Thrombosis

Central venous catheter (CVC) is useful for prolonged intravenous treatment, but not without risk. This is a case report of a 21-year-old male with a rare incident of CVC misplacement from the right subclavian vein to the left. The misplacement caused severe discomfort and possibly secondary thrombosis (VT) of deep cervical veins. The CVK was removed, and the patient was treated with rivaroxaban for three months, which made him recover without sequelae. VT, due to CVC, can cause a potentially life-threatening pulmonary embolism. CVC placement should be controlled by X-ray, and abnormal findings should be communicated.

Topics: Catheterization, Central Venous; Factor Xa Inhibitors; Humans; Male; Medical Errors; Radiography, Thoracic; Rivaroxaban; Subclavian Vein; Venous Thrombosis; Young Adult

There is a lack of consensus regarding optimal anticoagulation regimen and duration for inferior vena cava (IVC) thrombus due to the paucity of clinical evidence. A case of IVC thrombus treated with 3 months of rivaroxaban therapy is reported.. Fifty-two-year-old male Caucasian presented following a motorcycle accident, with multiple left rib fractures requiring emergent amputation surgeries. During the hospitalization, he developed IVC thrombosis and completed 3 months of rivaroxaban treatment without any complication. The Doppler images at 6-week, 3-month and 6-month follow-up appointments showed no IVC thrombosis.. This is the first case of IVC thrombosis successfully treated with rivaroxaban. Further case series and clinical studies are needed to guide the use of direct oral anticoagulants for IVC thrombosis.

Topics: Administration, Oral; Factor Xa Inhibitors; Follow-Up Studies; Humans; Male; Middle Aged; Multiple Trauma; Rivaroxaban; Time Factors; Vena Cava, Inferior; Venous Thrombosis

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

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

Topics: Humans; Liver Cirrhosis; Mesenteric Ischemia; Mesenteric Veins; Portal Vein; Rivaroxaban; Thrombosis; Venous Thrombosis

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

Peripherally inserted central catheters (PICCs) are frequently used for prolonged drug administration, but their use is commonly complicated by the development of upper extremity deep venous thrombosis (UEDVT) requiring anticoagulation. Here, we compared the efficacy and safety profile of rivaroxaban (20 mg/d) with low molecular weight (LMW) heparin and vitamin K antagonists in the treatment of PICC-associated UEDVT.. Patients (N = 84) with PICC-associated UEDVT were studied. All had UEDVT identified by ultrasound scanning. Further ultrasound images were obtained at 1, 2, and 3 months after the start of treatment. Forty-four patients were treated with rivaroxaban and 40 with initial LMW heparin and vitamin K antagonist with continuation of vitamin K antagonists alone once international normalized ratio was therapeutic FINDINGS: In the rivaroxaban group mean (SD) age was 51 (16) years and 57% were men, whereas in the other group respective values were 50 (16) years and 56%. All patients were receiving treatment for cancer. Resolution of thrombus had occurred in 53.5% at 1 month, 76.1% at 2 months, and 92.6% at 3 months in the rivaroxaban-treated patients. Corresponding values in the LMW heparin/vitamin antagonist-treated patients were 34.2%, 55.5%, and 88.5%, respectively. Differences between groups were significant at 1 month (P < 0.01) and 2 months (P < 0.05). There were no major bleeds in either group, and cumulative bleeding rates by 3 months were 7.3% in the rivaroxaban group and 11.4% in the LMW heparin/vitamin K antagonist group.. Rivaroxaban led to faster resolution of PICC-associated UEDVT than LMW/vitamin K antagonists without any increase in bleeding.

Topics: Adult; Aged; Blood Coagulation; Catheterization, Peripheral; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Rivaroxaban; Upper Extremity; Venous Thrombosis; Vitamin K

Role of prophylactic anticoagulation in acutely ill medical patients has been extensively probed with the development of guidelines which made it convenient for the physicians to adopt a particular anticoagulation regimen for thromboprophylaxis. Intermingled with the guidelines are the development of modern anticoagulants like direct factor Xa inhibitors which are being studied for their role in the prevention of venous thromboembolism (VTE) in medically ill patients and have been concluded so far with the positive note. We are going to discuss a case of a patient who was admitted in the medical ICU with hospital acquired pneumonia. As her immediate risk of VTE was low (Wells criteria), she was advised mechanical measures to prevent VTE along with continuation of rivaroxaban therapy which had already been prescribed for her avalvular atrial fibrillation. While mechanically ventilated, she developed pulmonary venous thromboembolism. It is the first case report of VTE in adequately anticoagulated patient with rivaroxaban.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Critical Illness; Factor Xa Inhibitors; Humans; Respiration, Artificial; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Endovenous heat-induced thrombosis (EHIT) and deep venous thrombosis (DVT) are well-known complications after superficial endovenous thermoablation. We investigated the efficacy of rivaroxaban in preventing EHIT and DVT after endovenous laser ablation (EVLA).. We retrospectively analyzed a consecutive series of patients presenting with truncal varicosis class C. Between February 2009 and December 2015, 391 patients (473 limbs) were treated with EVLA of the truncal saphenous vein. The primary end point occurred in 13 of 166 (7.8%) and 14 of 225 (6.2%) after 1 week and in 13 of 166 (7.8%) and 15 of 225 (6.7%) after 4 weeks comparing the rivaroxaban and fondaparinux groups (P = .659). EHIT class 1 was observed in 20 patients (5.1%) and EHIT class 2 in five (1.3%). No patients had EHIT class 3 or 4. The incidence of DVT was one of 166 (0.6%) in the rivaroxaban group and two of 225 (0.9%) in the fondaparinux group (P = .750). Minor bleeding events occurred in 17 of 166 patients (10.2%) and in 20 of 225 patients (8.9%), respectively (P = .652). No major bleeding events were observed. Paresthesia was observed in 12.5% in the rivaroxaban group and in 17.8% in the fondaparinux group. No skin burns were observed.. Rivaroxaban offers an oral medication approach showing no difference in preventing EHIT and DVT compared with fondaparinux, without increased bleeding risk.

Topics: Administration, Cutaneous; Administration, Oral; Endovascular Procedures; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Laser Therapy; Male; Middle Aged; Polysaccharides; Retrospective Studies; Rivaroxaban; Saphenous Vein; Treatment Outcome; Varicose Veins; Venous Insufficiency; Venous Thrombosis

Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the accumulation of inflammatory factors in the lesions in venous thrombus. Matrix metalloproteinase (MMP) expression and activity were downregulated in rivaroxaban-treated rats with deep venous thrombus. Rivaroxaban inhibited the elasticity of the extracellular matrix and collagen-elastin fibers. On the whole, these results indicate that rivaroxaban attenuates deep venous thrombus through MMP-9-mediated NF-κB signaling pathway.

Topics: Animals; Disease Models, Animal; Fibrinolysis; Humans; Matrix Metalloproteinase 9; NF-kappa B; Rats; Rivaroxaban; Signal Transduction; Veins; Venous Thromboembolism; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is immune-mediated. It occurs more frequently with unfractionated heparin (UFH) than with low molecular weight heparins (LMWH). It is associated with thromboembolic rather than hemorrhagic events, as opposed to thrombocytopenia of other etiologies. The key in therapy is the cessation of heparin and the start of another anticoagulant. We report a 58 years old female with HIT secondary to the use of Enoxaparin who was successfully managed with Rivaroxaban. Our goal is to report a novel therapy and provide the evidence that supports its use.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Heparin; Humans; Middle Aged; Risk Factors; Rivaroxaban; Thrombocytopenia; Treatment Outcome; Venous Thrombosis

Cutaneous leukocytoclastic vasculitis (LCV) is type of small vessel vasculitis that commonly presents as palpable purpura involving the lower extremities and buttocks. Approximately half of cases are idiopathic, but the disease may be triggered by infection, drug reaction, inflammatory disease, or other causes. We report a case of leukocytoclastic vasculitis secondary to the novel anticoagulant rivaroxaban (Xarelto®).

Topics: Adult; Arm; Biopsy; Factor Xa Inhibitors; Female; Humans; Leg; Lymphedema; Rivaroxaban; Vasculitis, Leukocytoclastic, Cutaneous; Venous Thrombosis

Thromboprophylaxis is a controversial and challenging topic in joint replacement surgery. Mechanical prophylaxis in combination with the use of anticoagulants have been shown to have greater efficacy than single modalities. But the early use of anticoagulants has the potential to increases the risk of postoperative bleeding. The purpose of this study was to evaluate the thromboprophylactic effects of sequential combined method using early-mechanical compression with delayed rivaroxaban in total knee arthroplasty. A retrospective cohort study, including 369 patients receiving simultaneous combined mechanical and pharmacological thromboprophylactic modality and 385 patients receiving sequential combined modality with early-mechanical compression treatment followed by rivaroxaban 2 days later after primary total knee arthroplasty surgery was conducted. The incidence rates of proximal and distal deep vein thrombosis (DVT) on the 2nd day and the 5th week and the volume of wound drainage were compared postoperatively. On the 2nd postoperative day, the incidence rates of proximal and distal DVT in the sequential group (1.56, 4.16%) had no significant difference compared with those (1.08, 3.25%) in the simultaneous group (

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Combined Modality Therapy; Female; Humans; Incidence; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Postoperative Care; Postoperative Complications; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thrombosis

Topics: Blood Coagulation; Blood Coagulation Tests; Factor Xa Inhibitors; Humans; Rivaroxaban; Venous Thrombosis

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

Stroke is a clinically important problem. A left atrial thrombus is known as a cause of ischaemic stroke. A pulmonary vein thrombus (PVT) is thought to be rare; however, PVT is common in elderly patients. Additionally, images of PVT with transoesophageal echocardiography (TEE) following treatment have not been well contrasted with that from either 64 or 80-slice multidetector CT (80-MDCT). The images of such changes depicted by TEE remain unknown. An 87-year-old man with hypertension was examined by 80-MDCT and TEE to check the cardiac thrombus. Although 80-MDCT did not depict the thrombus, TEE depicted the thrombus in the left atrium and right lower pulmonary vein (RLPV) clearly. After 6 months of rivaroxaban treatment, the thrombus in the RLPV decreased slightly and the thrombus in the left atrium became small and lucent, as estimated with TEE. Rivaroxaban decreased the size of the thrombus and changed the quality of the thrombus.

Topics: Aged, 80 and over; Drug Administration Schedule; Echocardiography, Transesophageal; Factor Xa Inhibitors; Heart Atria; Heart Diseases; Humans; Male; Multidetector Computed Tomography; Pulmonary Veins; Pulmonary Veno-Occlusive Disease; Rivaroxaban; Thrombosis; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Clinical Trials as Topic; Humans; Rivaroxaban; Venous Thrombosis

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

Topics: Humans; Liver Cirrhosis; Liver Diseases; Portal Vein; Rivaroxaban; Thrombosis; Venous 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

For many years, the standard of care for patients diagnosed with deep vein thrombosis (DVT) has been low-molecular-weight heparin (LMWH) bridging to an oral Vitamin-K antagonist (VKA). The availability of new non-VKA oral anticoagulants (NOAC) agents as monotherapy may reduce the likelihood of hospitalization for DVT patients.. To compare hospital visit costs of DVT patients treated with rivaroxaban and LMWH/warfarin.. A retrospective claim analysis was conducted using the MarketScan Hospital Drug Database for care provided between January 2011 and December 2013. Adult patients using rivaroxaban or LMWH/warfarin with a primary diagnosis of DVT during the first day of a hospital visit were identified (i.e., index hospital visit). 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. The hospital-visit cost difference between these groups was evaluated for the index hospital visit, as well as for total hospital-visit costs (i.e., including index and subsequent hospital visit costs).. All rivaroxaban users (n = 134) in the database were well-matched with four LMWH/warfarin users (n = 536). The mean hospital-visit costs were $5257 for the rivaroxaban cohort and $6764 in the matched-cohort of patients using LMWH/warfarin. The $1508 cost difference was statistically significant between cohorts (95% CI = [-$2296; -$580]; p-value = 0.002). Total hospital-visit costs were lower for rivaroxaban compared to LMWH/warfarin users within 1, 2, 3, and 6 months after index visit (significantly lower within 1 and 3 months, p-values <0.05) LIMITATIONS: Limitations were inherent to administrative-claims data, completeness of baseline characteristics, adjustments restricted to observational factors, and lastly the sample size of the rivaroxaban cohort.. The availability of rivaroxaban significantly reduced the costs of hospital visits in patients with DVT treated with rivaroxaban compared to LMWH/warfarin.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Female; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Insurance Claim Review; Male; Middle Aged; Residence Characteristics; Retrospective Studies; Rivaroxaban; Sex Factors; Socioeconomic Factors; Venous Thrombosis; Warfarin

Topics: Blood Coagulation Factors; Factor Xa Inhibitors; Humans; Male; Middle Aged; Rivaroxaban; Venous Thrombosis

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

Spontaneous effort-induced thrombosis is a rare but reported phenomena that was originally described over 100 years ago. The pathogenesis of this thrombosis arises from an abnormality of the thoracic outlet usually combined with a history of physical activity that includes repetitive arm motions, usually of the dominant hand. We present the case of an adolescent patient who presented to a pediatric emergency department with progressive pain, discoloration, and swelling of the shoulder of his nondominant hand. The pain became acutely worse with graying appearance of his arm. The patient was diagnosed with spontaneous thrombosis of the upper extremity extending from the left subclavian vein extending to the axillary vein. Treatment of this patient included aggressive anticoagulation, thrombolysis, and costectomy.

Topics: Anticoagulants; Arm; Diagnosis, Differential; Enoxaparin; Factor Xa Inhibitors; Follow-Up Studies; Humans; Male; Ribs; Rivaroxaban; Soccer; Subclavian Vein; Thrombolytic Therapy; Treatment Outcome; Upper Extremity Deep Vein Thrombosis; Venous Thrombosis; Weight Lifting; Young Adult

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: Early Detection of Cancer; Factor Xa Inhibitors; Humans; Male; Middle Aged; Neoplasms; Referral and Consultation; Rivaroxaban; Venous Thrombosis

Periprosthetic joint infection is a disastrous complication after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The use of certain agents to prevent deep vein thrombosis after arthroplasty has been linked to an increased risk of adverse effects including wound drainage and infection. Adverse effects of one alternative, rivaroxaban, was studied in a single community hospital.. International Classification of Diseases, Clinical Modification 9 codes were used to identify primary THAs and TKAs in an administrative database at one large-volume community hospital performed in 2012. Patients were divided into 2 groups: the study group received rivaroxaban, whereas the control group received another form of chemical thromboprophylaxis for at least 2 weeks postoperative. Demographics, risk factors, and illness severity scores were collected for each group. The primary measured outcome was the incidence of deep surgical site infection (SSI) within 30 days postoperative.. A total of 639 TKA or THA patients were included, with 159 patients who received rivaroxaban and 480 who received another form of chemical thromboprophylaxis. There were no significant differences between groups regarding demographics, risk factors, or illness severity scores. Incidence of early deep SSI in the rivaroxaban group was higher than in the control group (2.5% vs 0.2%; P < .015).. The use of rivaroxaban for thromboprophylaxis led to a significantly increased incidence of deep SSI in a continuous series of patients undergoing primary THA and TKA in a single institution.

Topics: Aged; Anticoagulants; Arthritis, Infectious; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Hip Prosthesis; Hospitals, Community; Humans; Incidence; Knee Prosthesis; Male; Middle Aged; Postoperative Period; Retrospective Studies; Risk Factors; Rivaroxaban; Severity of Illness Index; Surgical Wound Infection; Venous Thrombosis

Topics: Computed Tomography Angiography; Embolization, Therapeutic; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Melena; Middle Aged; Pulmonary Disease, Chronic Obstructive; Risk Factors; Rivaroxaban; Treatment Outcome; Vascular Malformations; Venous Thrombosis

Selective inhibitors of factor Xa (FXa) are widely recognized as useful therapeutic tools for stroke prevention in non-valvular atrial fibrillation or venous thrombosis. Thrombin, which is rapidly generated from pro-thrombin through the activation of factor X to FXa, acts as a potent activator of human platelets. Thus, the reduction of thrombin generation by FXa inhibitor eventually causes a suppressive effect on platelet aggregation. However, little is known whether FXa inhibitors directly affect the function of human platelets. We have previously reported that collagen induces the phosphorylation of heat shock protein 27 (HSP27), a low-molecular weight heat shock protein via Rac-dependent activation of p44/p42 mitogen-activated protein (MAP) kinase in human platelets, eventually resulting in the release of HSP27. In the present study, we investigated the direct effect of FXa inhibitor on the collagen-induced human platelet activation. Rivaroxaban as well as edoxaban significantly reduced the collagen-induced phosphorylation of both HSP27 and p44/p42 MAP kinase without affecting the platelet aggregation. Rivaroxaban significantly inhibited the release of phosphorylated HSP27 from collagen-stimulated platelets but not the secretion of platelet derived growth factor-AB. In patients administrated with rivaroxaban, the collagen-induced levels of phosphorylated HSP27 were markedly diminished after 2 days of administration, which failed to affect the platelet aggregation. These results strongly suggest that FXa inhibitor reduces the collagen-stimulated release of phosphorylated HSP27 from human platelets due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase.

Topics: Aged; Blood Platelets; Collagen; Factor Xa Inhibitors; Female; Healthy Volunteers; HSP27 Heat-Shock Proteins; Humans; Male; MAP Kinase Signaling System; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Platelet Activation; Platelet Aggregation; Pyridines; Rivaroxaban; Thiazoles; Venous Thrombosis

The direct inhibitors of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently used in patients with venous thrombosis of the lower or upper limbs or with pulmonary embolism. However, the use of these direct oral anticoagulants (DOACs) in subjects with abdominal or cerebral venous thrombosis is more contentious due to the paucity of available data. In a few case reports and small series of patients hitherto published, the DOACs showed good efficacy and safety, supporting an extension of their use to these rare conditions. Thus, prospective cohort studies and randomized controlled trials have been set up. In this article, we review the published clinical experience with DOACs in rare venous thrombosis, and provide updated information on ongoing clinical trials.

Topics: Anticoagulants; Dabigatran; Humans; Pyrazoles; Pyridones; Rivaroxaban; Venous Thrombosis

To assess the effectiveness of anticoagulant therapy (ACT) for the treatment of patients with deep venous thrombosis (DVT) of the lower extremities.. The study considered ultrasonic characteristics of lysis of the proximal part of thrombus: localization and nature of venous thrombosis, the length and diameter of the proximal floating part of the thrombus, and duration of the venous thrombosis. Depending on the ACT options patients were divided into 3 groups: Group 1 (18 patients) received rivaroxaban, group 2 (19 patients) received enoxaparin sodium with subsequent transition to warfarin, and 3 group (19 patietns) received enoxaparin sodium, followed by administration of rivaroxaban.. Treatment with rivaroxaban was preferable over standard ACT with enoxaparin/warfarin with regards to the lysis of thrombus when duration of thrombosis did not exceed 10 days. In 10.5% of patients who received warfarin flotation of thrombi remained for 14 days; the length of the floating part of the thrombi did not exceed 3 cm. Such circumstances and inability to reach a therapeutic INR value required cava filter placement. Treatment with enoxaparin sodium followed by the administration of rivaroxaban was found to be the most efficient ACT regimen as there was no negative dynamics of ultrasound characteristics of lysis of thrombi at any duration of the disease.. Цель исследования - провести оценку эффективности антикоагулянтной терапии (АКТ) при лечении больных тромбозом глубоких вен (ТГВ) нижних конечностей. Материал и методы. Учитывались ультразвуковые характеристики лизиса проксимальной части тромба: локализация и характер венозного тромбоза, длина и диаметр флотирующей верхушки тромба, а также давность венозного тромбоза. В соответствии с намеченной тактикой АКТ пациенты разделены на 3 группы: 1-я группа (18 человек) получала ривароксабан, 2-я группа (19 человек) - эноксапарин натрия с последующим переходом на варфарин и 3-я группа (19 человек) получала эноксапарин натрия с последующим назначением ривароксабана. Результаты. Установлено, что ривароксабан предпочтительнее стандартной АКТ эноксапарином/варфарином в лизисе тромбов при давности венозного тромбоза менее 10 сут. На фоне варфаринотерапии в 10,5% случаев сохранялась флотация до 3 см более 14 дней, что при отсутствии достижения терапевтического значения МНО потребовало имплантации кава-фильтра. Схемой АКТ, при которой отсутствовала отрицательная ультразвуковая динамика лизиса тромба на любом сроке заболевания, оказалось применение эноксапарина натрия с последующим назначением ривароксабана.

Topics: Aged; Anticoagulants; Drug Monitoring; Enoxaparin; Female; Humans; International Normalized Ratio; Lower Extremity; Male; Middle Aged; Rivaroxaban; Thrombosis; Treatment Outcome; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Adult; Aerospace Medicine; Collateral Circulation; Combined Modality Therapy; Edema; Emergencies; Female; Heparin; Humans; Leg; Livedo Reticularis; Low Back Pain; Mobility Limitation; Phlebography; Rivaroxaban; Stockings, Compression; Tachycardia, Sinus; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Ultrasonography, Doppler; Vena Cava, Inferior; Venous Thrombosis

Topics: Aged; Biopsy; Drug-Related Side Effects and Adverse Reactions; Exanthema; Humans; Male; Methylprednisolone; Neutrophils; Rivaroxaban; Skin; Vasculitis, Leukocytoclastic, Cutaneous; Venous Thrombosis; Withholding Treatment

Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Renal Dialysis; Rivaroxaban; Thromboembolism; Venous Thrombosis

Topics: Adult; beta-Thalassemia; Echocardiography; Female; Humans; Ovary; Peripartum Period; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Ventricular Dysfunction, Left

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: Adult; Aged; Anticoagulants; Antithrombins; Arginine; Dabigatran; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Pipecolic Acids; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Sulfonamides; Venous Thrombosis

The CIVIQ questionnaire was used to evaluate quality of life of patients presenting with deep vein thrombosis of lower limbs in different variants of anticoagulant therapy. The study included a total of 170 patients who were depending on the variant of anticoagulant therapy subdivided into 3 groups: Group One (comprising 48 patients) taking rivaroxaban as monotherapy; Group Two (consisting of 73 subjects) receiving low molecular weight heparin (enoxaparin sodium) followed by adjusting the warfarin dose, and Group Three (including 49 patients) receiving low molecular weight heparin (enoxaparin sodium) followed by rivaroxaban. The total value of the level of quality of life in all groups showed a tendency towards restoration. However, patients taking warfarin during the follow-up period were found to have negative dynamics by the 6th month of treatment. It was revealed that quality of life on all parameters was higher in patients taking rivaroxaban and lower in those taking warfarin. The parameters of the physical component of health turned out to depend upon the degree of recanalization of the thrombus. After 6 months of anticoagulant therapy patients taking rivaroxaban (Groups One and Three) were found to have good recanalization in 87.5 and 87.7% of cases, respectively, while in Group Two being observed in 54.8% of patients only. Taking an anticoagulant at a fixed dose not requiring laboratory control (rivaroxaban) increases patient compliance, thus leading to improvement of both mental and social wellbeing.. С помощью опросника CIVIQ исследовано качество жизни больных с тромбозом глубоких вен нижних конечностей при различных вариантах антикоагулянтной терапии. В исследование включено 170 больных, которые в зависимости от варианта антикоагулянтной терапии были разделены на 3 группы: 1 группа (48 человек) – больные принимали ривароксабан в качестве монотерапии; 2 группа (73 человека) – пациенты получали низкомолекулярный гепарин (эноксапарин натрия) с последующим подбором дозы варфарина; 3 группа (49 человек) – пациенты получали низкомолекулярный гепарин с последующим приёмом ривароксабана. Суммарное значение уровня качества жизни во всех группах имело тенденцию к восстановлению. Однако, у пациентов, принимавших варфарин в амбулаторном периоде, наблюдалась отрицательная динамика к 6 месяцу лечения. Выявлено, что качество жизни по всем параметрам выше у больных, принимающих ривароксабан, чем у получавших лечение варфарином. Показатели физического компонента здоровья зависят от степени реканализации вен. Через 6 месяцев антикоагулянтной терапии у больных, принимавших ривароксабан (1 и 3 группы), хорошая реканализация отмечена в 87,5 и 87,7% случаев соответственно, а во 2 группе – только у 54,8% пациентов. Приём антикоагулянта в фиксированной дозе, не требующей лабораторного контроля (ривароксабан), повышает приверженность пациентов к лечению, что приводит к улучшению качества жизни.

Topics: Adult; Aged; Anticoagulants; Drug Administration Schedule; Enoxaparin; Female; Humans; Lower Extremity; Male; Middle Aged; Quality of Life; Rivaroxaban; Surveys and Questionnaires; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency; Venous Thrombosis; Warfarin

Topics: Antiphospholipid Syndrome; Bipolar Disorder; Disease Management; Factor Xa Inhibitors; Female; Heart Valve Prosthesis Implantation; Humans; Middle Aged; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Rivaroxaban; Stroke; Treatment Outcome; Venous Thrombosis

Topics: Ambulatory Care; Clinical Protocols; Critical Pathways; Emergency Service, Hospital; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Pyrazoles; Pyridones; Rivaroxaban; Venous Thrombosis

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

Following orthopaedic surgery, a 56-year-old woman developed heparin-induced thrombocytopenia (HIT), complicated by extensive proximal deep vein thrombosis. The patient did not respond to multiple conventional therapies; however, a prompt treatment response occurred after starting rivaroxaban at standard dosing. This case represents the first documentation of efficacy for rivaroxaban in the setting of treatment refractory HIT and strengthens the limited existing evidence for this agent in HIT.

Topics: Anticoagulants; Drug Resistance; Factor Xa Inhibitors; Female; Heparin; Humans; Middle Aged; Orthopedic Procedures; Postoperative Complications; Rivaroxaban; Thrombocytopenia; Venous Thrombosis

Evidence from clinical trials shows rivaroxaban to be effective for the treatment of deep vein thrombosis. Switching to rivaroxaban following failure of indirect anticoagulants in deep vein thrombosis has not been demonstrated in a real-life setting.. A 43-year-old white woman was switched from warfarin to rivaroxaban for the treatment of thrombosis of her right common femoral vein after saphenectomy. The reason for the switch was due to the instability of anti-coagulation therapy with vitamin K antagonists over a period of 3 months during which she did not reach the "therapeutic range" of prothrombin time-international normalized ratio. The ineffectiveness of the conventional oral anticoagulant was confirmed by persistence of moderate-high values of fibrin D dimers (780 ng/ml) and by residual vein thrombosis at an ultrasound examination. Objectively, her right leg appeared to be still edematous and warm and pain was elicited by deep palpation. Rivaroxaban was administered after warfarin discontinuation (prothrombin time-international normalized ratio = 1.43) at a dosage of 15 mg every 12 hours for 3 weeks, followed by 20 mg once daily for 3 months. After this period, her objective symptoms significantly improved, with reduction of edema of her lower limb and pain relief. Her fibrin D dimer values returned to normal (210 ng/ml). An ultrasound showed recanalization of the obstructed venous segment.. In this case report, a switch to rivaroxaban from warfarin was shown to be effective and safe for the treatment of postoperative deep vein thrombosis, whereas standard oral anticoagulation therapy, which required dose adjustments over a period of 3 months, was not able to stabilize the therapeutic range of prothrombin time-international normalized ratio nor improve our patient's outcome.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Female; Humans; Lower Extremity; Postoperative Complications; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

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

Cirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may aggravate portal hypertension, and it can lead to hepatic decompensation. The international guideline recommends for anticoagulation treatment to be maintained for at least 3 months in all patients with acute PVT. Low-molecular-weight-heparin and changing to warfarin is the usual anticoagulation treatment. However, warfarin therapy is problematic due to a narrow therapeutic window and the requirement for frequent dose adjustment, which has prompted the development of novel oral anticoagulants for overcoming these problems. We report a 63-year-old female who experienced complete resolution of recurrent acute PVT in liver cirrhosis after treatment with rivaroxaban.

Topics: Administration, Oral; Factor Xa Inhibitors; Female; Humans; Liver Cirrhosis; Middle Aged; Portal Vein; Recurrence; Rivaroxaban; Tomography, X-Ray Computed; Venous Thrombosis

In Ireland, Warfarin is the primary anticoagulant prescribed in the secondary prevention of provoked DVT. We completed a comprehensive cost analysis of a trial group of 24 patients treated with Rivaroxaban (between November 2013 and December 2014), versus a control group treated with Warfarin (between January 2008 and November 2013). The groups were matched for gender (3/7 M/F ratio), DVT type (5 proximal, 19 distal DVTs), provoking factor (20 traumatic, 4 atraumatc), and age. We calculated the cost for each group based on drug administration and clinic costs (labour, sample analysis, and additional costs). Warfarin patients attended clinic 14.58 times; Rivaroxaban patients attended 2.92 times. Overall, the cost per patient on Rivaroxaban is €273.30 versus €260.68 with warfarin. This excludes patient costs which would further increase cost of Warfarin therapy.

Topics: Anticoagulants; Costs and Cost Analysis; Drug Costs; Factor Xa Inhibitors; Female; Humans; Ireland; Male; Rivaroxaban; Secondary Prevention; Venous Thrombosis; Warfarin

Topics: Aged; Blood Coagulation; Factor Xa Inhibitors; Female; Heparin; Heparin Antagonists; Humans; Kidney Failure, Chronic; Male; Middle Aged; Morpholines; Peripheral Vascular Diseases; Platelet Count; Renal Dialysis; Rivaroxaban; Thiophenes; Thrombocytopenia; Venous Thrombosis

Rivaroxaban, a new oral anti-Xa agent, has been approved for use without routine monitoring, but the lack of a predictable drug level measurement may hinder the management of anticoagulated patients. The aims of the project were to correlate a Anti-Factor Xa assay using commercial calibrators and controls (Riva Activity) with serum drug levels analyzed by HPLC-MS/MS (Riva MS) in patients currently receiving rivaroxaban, and secondly, to correlate the PT/PTT, thrombin generation (CAT assay) and Thromboelastograph (TEG) with the Riva activity and Riva MS.. Recruited patients receiving rivaroxaban prospectively had a total of 3 blood samples taken at least 2 hours apart. Plasma was divided for measurement of PT/PTT, Riva activity, rivaroxaban HPCL-MS/MS, and thrombin generation. TEG activity was measured at one random time point for each patient. Correlation and linear regression evaluations were used to compare the different assays.. The cases were 22 patients on rivaroxaban, age 56+12.6, and 10 healthy controls. There was a strong correlation between Riva activity compared to serum Riva MS (r=0.99). We found a statistically significant correlation between PT/INR compared to serum measurements of Riva MS (r=0.68) and anti-Xa activity (r=0.69). The peak (r=-0.50) and lag time (r=0.57) CAT correlated with Riva MS measurements. There was no correlation between Riva MS and PTT, TEG R, TEG MA, Endogenous Thrombin potential.. Riva anti-factor Xa activity assay measured with commercial calibrators and controls provides a reliable assessment of rivaroxaban serum levels for patients requiring measurement of anticoagulant activity. Correlation with other coagulation tests is not sufficiently strong to be used clinically.

Topics: Adult; Cohort Studies; Factor Xa Inhibitors; Female; Humans; Male; Mass Spectrometry; Morpholines; Prospective Studies; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Aged; Amyotrophic Lateral Sclerosis; Anticoagulants; Female; Follow-Up Studies; Humans; Male; Middle Aged; Rivaroxaban; Venous Thrombosis

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

Topics: Aged, 80 and over; Antibodies; Anticoagulants; Blood Platelets; Dalteparin; Female; Fondaparinux; Hip Fractures; Hirudins; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Morpholines; Peptide Fragments; Platelet Count; Polysaccharides; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombocytopenia; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition and it is associated with increased in vivo thrombin generation that needs to be treated with non-heparin anticoagulants such as direct thrombin inhibitors (DTIs). DTIs require parenteral administration and are associated with a non negligible risk of major bleeding. We describe a case of HIT treated with rivaroxaban, a direct oral factor Xa inhibitor which could be used to inhibit the generation of thrombin, instead of DTIs. A 68 year-old man with a thrombosis confined to the internal gastrocnemius and soleal veins developed HIT during enoxaparin 80 mg twice a day. Enoxaparin was stopped and rivaroxaban 20 mg once a day was started. Platelet count returned to base line after 6 days from enoxaparin withdrawal. After 3 months rivaroxaban was stopped and the patient had an uneventful course. This case report supports the hypothesis that rivaroxaban may be candidate for treatment of HIT, and larger studies are justified.

Topics: Administration, Oral; Aged; Heparin; Humans; Male; Rivaroxaban; Thrombocytopenia; Venous Thrombosis

Topics: Adult; Antithrombin III Deficiency; Asparaginase; Delayed-Action Preparations; Humans; Male; Morpholines; Polyethylene Glycols; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

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: Adult; Factor Xa Inhibitors; Humans; Male; Recurrence; Rivaroxaban; Testicular Neoplasms; Venous Thrombosis

Topics: Adult; Afibrinogenemia; Female; Humans; Rivaroxaban; Venous Thrombosis

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

Topics: Anticoagulants; Antiparkinson Agents; Biotransformation; Dizziness; Drug Interactions; Drug Substitution; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Indans; Male; Middle Aged; Parkinson Disease; Rivaroxaban; Trihexyphenidyl; Venous Thrombosis; Warfarin

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

Topics: Adult; Factor Xa Inhibitors; Female; Humans; Intracranial Thrombosis; Magnetic Resonance Angiography; Male; Rivaroxaban; Venous Thrombosis

To describe the population admitted in an emergency department of a teaching hospital for severe bleeding associated with direct oral anticoagulants (DOAC).. During a three-year period (2012-2014) patients older than 16 years were prospectively identified by haemorrhagic symptoms from computerised requests. At least one of the following criteria defined major haemorrhage: haemorrhagic shock, unstable haemodynamic, need for transfusion or haemostatic procedure, or a life threatening location.. Fifty four patients, 23 receiving dabigatran, 30 rivaroxaban and one apixaban were included, 2 in 2012, 35 in 2013 and 17 in 2014. Median age was 84 years (range 63-99) with a sex ratio of 1.16. Haemorrhagic complications were gastrointestinal (n=27), intracranial (n=12) or miscellaneous (n=15). Indication of DOAC was stroke prevention in atrial fibrillation in 49 cases and deep vein thrombosis in 5 cases. Hospitalization was required for 45 patients (83%) with a mean length of stay of 8.5 days. Sixteen patients needed intensive care. Reversal therapy was prescribed in 11 patients. At 1 month, overall mortality was 24%, reaching 41.7% for intracranial haemorrhage. Among surviving patients, DOAC was stopped in 10 cases, continued in 17 patients and switched for other antithrombotic in 17 patients.. Our study contributes to the post marketing surveillance of major haemorrhagic complications associated with DOAC. It takes part to the knowledge about the course of this severe event in emergencies. Careful awareness in risk benefit assessment, especially in elderly, is needed.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Emergency Service, Hospital; Female; Gastrointestinal Hemorrhage; Hemodynamics; Hemorrhage; Hemostasis; Humans; Intracranial Hemorrhages; Male; Middle Aged; Patient Admission; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Venous Thrombosis

To compare the efficacy and safety of 3 rivaroxaban regimen in patients with venous thromboembolism (VTE).. This is a retrospective study. Thirty three inpatients with VTE received rivaroxaban were divided into 3 groups, in which 16 patients were treated with 15 mg rivaroxaban twice daily for 21 days then followed by 20 mg once per day till 3 months (group 1), 9 patients were treated with 20 mg rivaroxaban once daily for 3 months (group 2), 8 patients were treated with 10 mg rivaroxaban once daily for 3 months. The reduction rate of D-Dimer on the third therapy day, the duration of D-Dimer normalization and hospital stay as well as symptom remission, the imaging assessment results after three months treatment, rate of recurrent VTE, bleeding, liver and kidney function were compared among the 3 groups.. The reduction rates of D-Dimer on the third therapy day were significantly higher ((46.12 ± 15.42) % vs. (26.59 ± 8.11) % and (25.55 ± 14.00) %, P = 0.02, P = 0.01), and the duration of D-Dimer normalization was significantly shorter ((17.9 ± 7.7) days vs. (24.1 ± 5.1) days and (26.3 ± 6.2) d, P = 0.03, P < 0.01) in group 1 than in group 2 and 3. There was one recurrent deep-vein thrombosis in group 3, one non-major bleeding in group 1 and group 3. Major bleeding or liver and kidney dysfunction were not observed in these patients.. Venous thromboembolism can be safely and effectively treated by rivaroxaban, and does of 15 mg twice daily for 21 days followed by 20 mg once daily for 3 months are superior to the other 2 tested therapy regimen in this patient cohort.

Topics: Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Length of Stay; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

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

The direct factor Xa inhibitor rivaroxaban is approved for venous thromboembolism (VTE) treatment in adults. However, in all phase-III trials children or adolescents have not been included. For under-aged VTE patients, current standard treatment consists of low molecular weight heparin or Vitamin K antagonists. Rivaroxaban could be an attractive alternative, however, no data on the pharmacokinetics (PK) of rivaroxaban in adolescents are currently available. PATIENT, METHODS: We report PK data for rivaroxaban derived from a girl (age:15 years), who presented three month after acute deep vein thrombosis, already receiving rivaroxaban therapy. In the steady state of rivaroxaban therapy (20 mg once daily), plasma levels at baseline, 3 and 6 hours after intake of rivaroxaban were measured to evaluate the pharmacokinetics and changes of global coagulation tests.. At baseline, a very low trough level of only 9.9 ng/ml rivaroxaban was found. At 3 hours, a peak concentration of 137.76 ng/ml rivaroxaban was observed with a rapid decrease within 6 hours after drug intake, when plasma levels of 34.45 ng/ml were measured. The patients INR and aPTT values reacted correspondingly.. Our data indicate that adolescents may exhibit lower peak and trough levels after rivaroxaban intake compared to adult patients, but seem to have similar PK curves during the elimination phase. While our case is the first published case of a successful VTE treatment in an under-aged patient, we strongly discourage the routine use of rivaroxaban in non-adult patients, until data from phase II and III trials are available.

Topics: Adolescent; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Metabolic Clearance Rate; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin + VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin + VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin + VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE.. A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin + VKA in adult patients treated for acute DVT or PE. All patients entered the model in the 'on-treatment' state upon commencement of oral rivaroxaban or enoxaparin + VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used.. Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin + VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model's results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin + VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin + VKA approximately 76% of the time.. The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. 'Real-world' applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system.. Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.

Topics: Anticoagulants; Cost-Benefit Analysis; Drug Therapy, Combination; Enoxaparin; Humans; Markov Chains; Middle Aged; Morpholines; Quality-Adjusted Life Years; Rivaroxaban; Thiophenes; United States; Venous Thrombosis; Vitamin K

Thrombosis is a major complication in diabetes mellitus. Since Factor Xa inhibitors are not only inhibit the coagulation system but also attenuate the leukocyte-endothelial interaction in acute inflammation models, the purpose of this study is to confirm the similar effects of rivaroxaban in a mouse model of type 2 diabetes mellitus.. In the treatment groups, either 5 or 10mg/kg of rivaroxaban dissolved in DMSO was orally given to KK-A(y) mice for 7 weeks (n=6 in each group). KK-A(y) mice fed by chow containing DMSO without rivaroxaban for 7 weeks were served for the control group (n=6). Following clamping of the mesenteric vein for 20 minutes, intravital microscopic observation of the intestinal microcirculation and the measurement of bleeding time after the needle puncture were carried-out. In another series, the calculation for blood cell counts and the measurement of blood fluidity using micro channel array flow analyzer (MC-FAN) were performed.. The initial event in the microvasculature is the leukocyte adhesion on endothelium. Then, the leukocytes make clusters and the platelets are involved in. These leukocyte-platelet conjugates aggregate and form thrombus. The leukocyte adherence and the microthrombus formation was significantly suppressed with the treatment of 10 mg/kg of rivaroxaban compared to the control group (P<0.05). While, the bleeding time was significantly extended with the treatment with 10mg/kg of rivaroxaban (P<0.01). The blood fluidity was maintained best with the treatment of 10 mg/kg rivaroxaban.. Rivaroxaban attenuates the leukocyte-platelet-endothelial interaction, which leads to the attenuation of microthrombus formation in a mouse model of diabetes mellitus.

Topics: Animals; Anticoagulants; Blood Coagulation; Cell Adhesion; Diabetes Mellitus, Type 2; Factor Xa Inhibitors; Female; Leukocytes; Mice; Microvessels; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

The new direct-acting anticoagulants such as dabigatran and rivaroxaban are usually not monitored but may be associated with haemorrhage, particularly where renal impairment occurs. They have no effective "antidotes". We studied 17 patients receiving dabigatran 150 mg twice daily for non-valvular atrial fibrillation and 15 patients receiving rivaroxaban 10 mg daily for the prevention of deep venous thrombosis after hip or knee replacement surgery. We assessed the effect of these drugs on commonly used laboratory tests and Calibrated Automated Thrombogram (CAT) using plasma samples. We also assessed effects in fresh whole blood citrated patient samples using thromboelastography on the TEG and the ROTEM. The efficacy of nonspecific haemostatic agents prothrombin complex concentrate (PCC), Factor VIII Inhibitor By-passing Activity (FEIBA) and recombinant activated factor VII (rVIIa) were tested by reversal of abnormal thrombin generation using the CAT. Concentrations added ex vivo were chosen to reflect doses normally given in vivo. Dabigatran significantly increased the dynamic parameters of the TEG and ROTEM and the lag time of the CAT. It significantly reduced the endogenous thrombin potential (ETP) and reduced the peak height of the CAT. Rivaroxaban did not affect the TEG and ROTEM parameters but did increase the lag time and reduce ETP and peak height of the CAT. For both drugs, these parameters were significantly and meaningfully corrected by PCC and FEIBA and to a lesser but still significant extent by rFVIIa. These results may be useful in devising a reversal strategy in patients but clinical experience will be needed to verify them.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Automation, Laboratory; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Dabigatran; Equipment and Supplies; Factor VII; Hemorrhage; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Stroke; Thiophenes; Thrombelastography; Thrombin; Thrombin Time; Venous Thrombosis; Withholding Treatment

Topics: Acute Disease; Anticoagulants; Drug Administration Schedule; Humans; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Rivaroxaban; Thiophenes; Tomography, X-Ray Computed; Venous Thrombosis

Topics: Adolescent; Adult; Blood Proteins; Female; Humans; Male; Morpholines; Mutation; Poland; Protein S; Protein S Deficiency; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Aged; Anticoagulants; Blood Coagulation; Female; Fibrinolysis; Gangrene; Humans; Lower Extremity; Morpholines; Neoplasms; Rivaroxaban; Thiophenes; Veins; Venous Thrombosis

Topics: Blood Proteins; Female; Humans; Male; Morpholines; Protein S; Protein S Deficiency; Rivaroxaban; Thiophenes; Venous Thrombosis

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

Topics: Adult; Aged; Anticoagulants; Female; Humans; Male; Mass Screening; Morpholines; Mutation; Prothrombin; Recurrence; Risk Factors; Rivaroxaban; Thiophenes; Thrombophilia; Treatment Outcome; Venous Thrombosis; Warfarin; Women's Health

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

The aim of the study was to make a preliminary assessment of the efficacy and safety of acute deep vein thrombosis (DVT) prolonged treatment with new oral anticoagulant rivaroxaban. Materials and methods. It was a prospective observational study included patents with instrumentally verified DVT admitted to the Department of Vascular Surgery of the Clinical Hospital n.1 President's Administration of Russian Federation. All patients were administrated to the initial treatment with low-molecular weight heparins during first 24-48 hours followed by overlapped therapy with vitamin-K-antagonists. Patients who rejected a standard therapy were offered an alternative oral anticoagulant rivaroxaban: 15 mg bid during first 3 weeks followed by 20 mg qd. The duration of therapy varied from 3 to 12 month and more depend on localization and clinical provocation of the thrombosis. The dynamic control was performed on 3rd, 6th, 9th and 12th month. The endpoints of the study were recurrent DVT verified with duplex ultrasound or pulmonary embolism (PE) and hemorrhagic complications. In the study were enrolled 30 patients aged 27-87 years (mean age - 59.0±16.8), 13 men and 17 women who had from 0 to 6 individual risk factors (average - 2.4±1.6). In 33.3% cases DVT was clinically provoked and in 66.7% - unprovoked. Results. There were no recurrent DVT or PE observed. Cumulative rate of bleeding was 13.3% (95% CI: 1.2-25.5%): 6.65% (95% CI: 1.8-21.3%) - minor bleeding , that did not need drug withdrawal or extra visit to the doctor, and 6.65% (95% CI: 1.8-21.3%) - clinically significant bleeding, that needed an unscheduled visit to the doctor, the temporary interruption of the therapy or medical intervention. Major bleeding were not identified. Bleeding were presented as hematuria, petechial skin hemorrhages and epistaxis. Conclusion. The study demonstrates feasibility and safety of the new oral anticoagulant rivaroxaban application in the prolonged treatment of acute DVT.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Blood Coagulation; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Moscow; Prospective Studies; Rivaroxaban; Secondary Prevention; Thiophenes; Time Factors; Treatment Outcome; Venous Thrombosis

Topics: Administration, Oral; Chromatography, High Pressure Liquid; Drug Overdose; Factor Xa; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Suicide, Attempted; Tandem Mass Spectrometry; Thiophenes; 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

Thrombosis of cerebral veins and sinus (cerebral venous thrombosis) is a rare stroke pathogenesis. Pharmaceutical treatment is restricted to heparin and oral anticoagulation with vitamin K antagonists (VKAs).. Between January 2012 and December 2013, we recorded data from our patients with cerebral venous thrombosis. The modified Rankin scale was used to assess clinical severity; excellent outcome was defined as modified Rankin scale 0 to 1. Recanalization was assessed on follow-up MR angiography. Patients were then divided into 2 treatment groups: phenprocoumon (VKA) and a novel factor Xa inhibitor. Clinical and radiological baseline data, outcome, recanalization status, and complications were retrospectively compared.. Sixteen patients were included, and 7 were treated with rivaroxaban. Overall outcome was excellent in 93.8%, and all patients showed at least partial recanalization. No statistical significant differences were found between the groups, except the use of heparin before start of oral anticoagulation (P=0.03). One patient in the VKA and 2 patients in the factor Xa inhibitor group had minor bleeding (P=0.55) within the median (range) follow-up of 8 months (5-26).. Factor Xa inhibitor showed a similar clinical benefit as VKA in the treatment of cerebral venous thrombosis. Further systematic prospective evaluation is warranted.

Topics: Adolescent; Adult; Aged; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Phenprocoumon; Rivaroxaban; Sinus Thrombosis, Intracranial; Thiophenes; Treatment Outcome; Venous Thrombosis; Young Adult

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Drug Substitution; Female; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Recurrence; Retrospective Studies; Rivaroxaban; Splenic Vein; Stroke; Thiophenes; Thromboembolism; Thrombophilia; Treatment Failure; Venous Thrombosis; Warfarin

Treatment with the new oral anticoagulant rivaroxaban can be associated with severe liver injury.. We report 2 patients with predominantly hepatocellular liver injury that had onset during treatment with rivaroxaban. Both were symptomatic, had massively elevated transaminase activity levels and hyperbilirubinemia, and fulfilled the criteria of Hy's law. Liver biopsy in 1 patient revealed centroacinar hepatocyte necrosis as the predominant finding. Both patients showed a rapid biochemical and clinical recovery after discontinuing rivaroxaban therapy. Between 2008 and 2013, 42 cases of liver injury possibly associated with rivaroxaban treatment have been reported to the Swiss Agency of Therapeutic Products (Swissmedic). Thirteen of these patients fulfilled the criteria of Hy's law.. Treatment with rivaroxaban can be associated with severe, symptomatic liver injury. Physicians should be aware of this adverse drug reaction. We propose rapid discontinuation of treatment with rivaroxaban in case of symptomatic liver injury and, taking into account its severity, avoiding reexposure.

Topics: Aged; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Fracture Fixation, Internal; Hepatocytes; Humans; Hyperbilirubinemia; Liver; Male; Middle Aged; Morpholines; Necrosis; Primary Prevention; Rivaroxaban; Thiophenes; Tibial Fractures; Venous Thrombosis

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

Topics: Aged; Disease Progression; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Poland; Rivaroxaban; Venous Thrombosis

In a 63-year-old cirrhotic patient, recanalisation of a partial portal vein thrombosis was achieved by a low dose of rivaroxaban (10 mg daily). After anticoagulant therapy was stopped, partial vein thrombosis recurred. Restarting rivaroxaban at a dose of 10 mg led to recanalisation. The patient did not suffer any complications; in particular no bleeding occurred during 8 months of treatment.

Topics: Anticoagulants; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Humans; Middle Aged; Morpholines; Portal Vein; Radiography; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

Topics: Adult; Anticoagulants; Blood Coagulation; Diosmin; Drug Combinations; Drug Monitoring; Female; Hesperidin; Humans; Male; Morpholines; Protein C Deficiency; Protein S Deficiency; Rivaroxaban; Thiophenes; Time; Treatment Outcome; Venous Thrombosis

Mesenteric vein thrombosis is a rare but potentially lethal cause of abdominal pain. It is usually caused by prothrombotic states that can either be hereditary or acquired. Testosterone supplementation causes an acquired prothrombotic state by promoting erythropoeisis thus causing a secondary polycythaemia. We report a case of a 59-year-old man with a history of chronic obstructive pulmonary disease (COPD) stage III, who presented with abdominal pain. Evaluation revealed an elevated haemoglobin and haematocrit, a superior mesenteric vein thrombosis on CT and a negative Janus kinase 2 mutation. The patient is currently being treated with 6 months of anticoagulation with rivaroxiban. Although a well-known side effect of testosterone is thrombosis, the present case is used to document in the literature the first case of mesenteric vein thrombosis due to secondary polycythaemia from Androgel in the setting of COPD.

Topics: Abdominal Pain; Diagnosis, Differential; Humans; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Morpholines; Polycythemia; Rivaroxaban; Testosterone; Thiophenes; Tomography, X-Ray Computed; Venous Thrombosis

To evaluate the safety and efficacy of rivaroxaban for prevention of deep vein thrombosis (DVT) in patients with preoperative abnormal D-dimer after total knee arthroplasty (TKA).. Between August and September 2013, 60 consecutive patients with varus knee osteoarthritis undergoing unilateral TKA were enrolled in the study. According to the preoperative D-dimer level, the patients were divided into 2 groups: D-dimer normal group (control group, n = 41) and D-dimer abnormal group (test group, n = 19). No significant difference was found in gender, age, body mass index, and preoperative knee range of motion between 2 groups (P > 0.05). All patients underwent conventional primary TKA and anticoagulation therapy with rivaroxaban to prevent DVT. The tourniquet use time, postoperative hospitalization time, and total hospitalization time were compared between 2 groups. At 1, 3, and 5 days after operation, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and D-dimer were measured. Wound complications and DVT were observed.. The postoperative hospitalization time of the test group was significantly longer than that of the control group (t = 2.327, P = 0.031), while the tourniquet use time and total hospitalization time showed no significant difference between 2 groups (P > 0.05). All the patients were followed up 6-8 months (mean, 7.2 months). Wound complications occurred in 3 cases (7.3%) of the control group and in 2 cases (10.5%) of the test group, showing no significant difference (χ2 = 0.175, P = 0.676). Color ultrasonography showed no pulmonary embolism and DVT at 6 weeks after TKA. There were significant differences in PT, TT, and FIB between at pre- and post-TKA in the same group, but no significant difference was found between 2 groups. The APTT and D-dimer had significant differences between at pre- and post-TKA in the same group, and between groups. There was no significant interaction effect between time and group for each index.. Preoperative abnormal D-dimer level should not be regarded as a contraindication for TKA. The risks of DVT and wound complications in patients with abnormal D-dimer level are similar to patients with normal D-dimer level using rivaroxaban administration after TKA. It is unnecessary to conventional monitor D-dimer and other coagulation and hemorrhage laboratory tests in the patients after TKA.

Topics: Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Humans; Knee Joint; Length of Stay; Morpholines; Osteoarthritis, Knee; Postoperative Complications; Postoperative Period; Preoperative Care; Prothrombin Time; Range of Motion, Articular; Rivaroxaban; Safety; Thiophenes; Venous Thrombosis

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

Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 μM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 μM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.

Topics: Animals; Anticoagulants; Crystallography, X-Ray; Drug Design; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Piperazines; Rats; Sulfonamides; Thrombin; Venous Thrombosis

Rivaroxaban is one of the new oral anticoagulants (NOACs). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis.

Topics: Anticoagulants; Humans; Morpholines; Pharmacists; Rivaroxaban; Thiophenes; Venous Thrombosis; Vitamin K

Topics: Acute Disease; Anticoagulants; Disease-Free Survival; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Neovascularization, Physiologic; Portal Vein; Recovery of Function; Regional Blood Flow; Rivaroxaban; Thiophenes; Ultrasonography, Doppler, Duplex; Venous Thrombosis

The new direct oral anticoagulants currently available are dabigatran, rivaroxaban and apixaban. These three drugs have been labeled in France for the prevention of venous thromboembolism after elective orthopaedic surgery including total hip or knee arthroplastly. Rivaroxaban is also labeled for the secondary prevention of thrombosis recurrence following an initial acute event. Pharmacologic properties of these drugs are reminded as well as the results of the main studies having conducted to their approval.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thrombosis

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

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Canada; Contraindications; Dabigatran; Drug Dosage Calculations; Drug Interactions; Humans; Morpholines; Postoperative Complications; Pyridines; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Prospective trials have shown that rivaroxaban thromboprophylaxis is superior over low-molecular-weight heparin (LMWH) in patients undergoing hip and knee replacement surgery. However, patients treated under trial conditions are different from unselected routine patients, which may affect efficacy and safety of thromboprophylaxis. The objective was to evaluate the efficacy and safety of rivaroxaban or LMWH thromboprophylaxis in unselected patients undergoing hip and knee replacement surgery in daily care. In a monocentric, retrospective cohort study in 5,061 consecutive patients undergoing hip and knee replacement surgery a comparison of LMWH (hospital standard in 2006-2007) and rivaroxaban (since 2009) was made with regard to rates of symptomatic VTE, bleeding and surgical complications and length of hospital stay. Rates of symptomatic VTE were 4.1 % (LMWH) and 2.1 % (rivaroxaban; p=0.005) with rates for distal DVT 2.5 vs. 1.1 % (p<0.001). Rates of major VTE were numerically higher with LMWH (1.7 vs. 1.1%, not statistically significant). Rates of major bleeding (overt bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban (2.9 vs. 7.0%; p<0.001). Rivaroxaban patients had fewer surgical complications (1.1 vs. 3.7%; p<0.001) and a shorter length of hospitalisation (8.3 days; 95% CI 8.1- 8.5 vs. 11.1 days; 10.7- 11.5; p< 0.001). We conclude that rivaroxaban thromboprophylaxis is more effective than LMWH in unselected patients undergoing hip and knee replacement surgery in daily care and that switching from LMWH to rivaroxaban could be beneficial. Prospective comparisons are warranted to confirm our findings.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Female; Fibrinolytic Agents; Germany; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Kaplan-Meier Estimate; Length of Stay; Logistic Models; Male; Middle Aged; Morpholines; Multivariate Analysis; Odds Ratio; Proportional Hazards Models; Registries; Retrospective Studies; Risk Factors; Rivaroxaban; Thiophenes; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis

Topics: Aged; Anticoagulants; Humans; Morpholines; Prothrombin Time; Rivaroxaban; Thiophenes; Venous Thrombosis

A novel series of potent and efficacious factor Xa inhibitors which possesses sulfoximine moiety as novel S4 binding element in anthranilamide chemotype has been identified. Lead optimization at this novel P4 group led to many potent factor Xa inhibitors with excellent anticoagulant activity in human plasma. Selected compounds were dosed orally in rats and checked for their ex vivo prothrombin time prolonging activity, which resulted in identification of compound 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(2-(diethylamino)acetyl)-S-methylsulfonimidoyl)benzamido)benzamide (18f). The detailed pharmacokinetic evaluation and subsequent metabolism study of 18f suggested the presence of an active metabolite. The compound 18f and its active metabolite 18b demonstrated excellent in vivo efficacy in both arterial and venous thrombosis model in rats and were found to be highly selective against related serine proteases. Based on this promising profile, compound 18f was selected for further evaluation.

Topics: Animals; Anticoagulants; Binding Sites; Disease Models, Animal; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Humans; Imines; Male; Models, Molecular; Molecular Structure; ortho-Aminobenzoates; Rats; Rats, Wistar; Reference Values; Serine Proteases; Serine Proteinase Inhibitors; Structure-Activity Relationship; Sulfoxides; Venous Thrombosis

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: Acute Coronary Syndrome; Altitude; Blood Coagulation Disorders; Coffee; Factor Xa Inhibitors; Heparin; Humans; Lipoproteins; Lymphatic Diseases; Morpholines; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis; Troponin; Venous Thrombosis; von Willebrand Diseases

Rivaroxaban is one of the novel oral direct factor Xa inhibitors, which is effective in preventing thromboembolic complications at fixed doses (i.e., once daily), without the need for dose adjustment according to laboratory monitoring. Nearly 60% of rivaroxaban is cleared from circulation by glomerular filtration, 30% of which is excreted as active drug. Therefore, as renal elimination plays a pivotal role in the metabolism of this drug, impairment of renal function may be important during anticoagulation with rivaroxaban over long periods of time. The assessment of the anticoagulant effect/concentration of rivaroxaban may thus be useful in special patient populations such as in the elderly and eldest, during acute diseases with concurrent dehydration, before surgery, during bleeding or thrombotic episodes, or to verify adherence to therapy. Rivaroxaban prolongs prothrombin time in a dose-dependent, linear fashion. Activated partial thromboplastin time (APTT) is also prolonged, but in an exponential manner. Substantial differences in test results might be generated by different thromboplastin and APTT reagents. One-step prothrombin-induced clotting time assay is sensitive to low concentrations of rivaroxaban. Chromogenic substrate assays specific for factor Xa are also sensitive to rivaroxaban. Several initiatives are currently ongoing to standardize the various methods to determine rivaroxaban in human plasma samples, some of which will be summarized in this article along with the dose-dependent effects of rivaroxaban on relevant coagulation parameters. Therefore, although rivaroxaban prolongs all coagulation assays used to assess the anticoagulant effects of most anticoagulants, the most specific assay cannot be identified at present. Moreover, clinical trials are needed to determine the relationship of assay results with bleeding or thrombotic complications.

Topics: Blood Coagulation; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Partial Thromboplastin Time; Prothrombin Time; Rivaroxaban; Thiophenes; Venous Thrombosis

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

The oral anticoagulant rivaroxaban is recommended for venous thromboembolic prophylaxis following lower limb arthroplasty. Concerns regarding high rates of wound complications following its use have prompted this multicenter comparison with low-molecular-weight heparins.. English hospital trusts that replaced a low-molecular-weight heparin with rivaroxaban for thromboprophylaxis in lower limb arthroplasty during 2009 were identified. Prospectively collected national data for these units were analyzed to determine the thirty-day rates of wound complications and major bleeding (cerebrovascular event or gastrointestinal hemorrhage) and the ninety-day rates of symptomatic deep venous thrombosis (proximal or distal), symptomatic pulmonary embolism, and all-cause inpatient mortality before and after the change to rivaroxaban. A total of 2762 patients prescribed rivaroxaban following knee or hip arthroplasty were compared with 10,361 patients prescribed a low- molecular weight heparin. Data were analyzed with use of odds ratios (ORs).. There were significantly fewer wound complications in the low-molecular-weight heparin group (2.81% compared with 3.85%; OR = 0.72, 95% confidence interval [CI] = 0.58 to 0.90; p = 0.005). There were no significant differences between the low-molecular-weight heparin and rivaroxaban groups in the rates of pulmonary embolism (0.55% compared with 0.36%; OR = 1.52, 95% CI = 0.78 to 2.98), major bleeding (OR = 0.73, 95% CI = 0.48 to 1.12), or all-cause mortality (OR = 0.93, 95% CI = 0.46 to 1.89). There were significantly more symptomatic deep venous thromboses in the low-molecular-weight heparin group (0.91% compared with 0.36%; OR = 2.51, 95% CI = 1.31 to 4.84; p = 0.004).. The rivaroxaban group had a higher wound complication rate and a lower deep venous thrombosis rate; there were no differences in symptomatic pulmonary embolism or all-cause mortality. Longer follow-up is needed to assess any potential relationship between wound complications and joint stiffness, latent infection, and limb consequences of deep venous thrombosis.

Topics: Age Distribution; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cerebral Hemorrhage; Cohort Studies; Confidence Intervals; Databases, Factual; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Morpholines; Odds Ratio; Postoperative Complications; Retrospective Studies; Risk Assessment; Rivaroxaban; Sex Distribution; Surgical Wound Infection; Survival Analysis; Thiophenes; Treatment Outcome; Venous Thrombosis; Wound Healing

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

Rivaroxaban is an oral anticoagulant that directly targets both free factor Xa and factor Xa in complex with its protein cofactor, factor Va, in the prothrombinase complex. It is approved in the United States for the prophylaxis of deep vein thrombosis and stroke in patients with atrial fibrillation; however, it also carries a black box warning regarding the risk of thrombosis after discontinuation of treatment. The purpose of this study was to determine the degree to which rivaroxaban, over a range of physiologically relevant free plasma concentrations, inhibits preassembled prothrombinase at a typical venous shear rate (100 s(-1)) and to determine the dynamics of rivaroxaban washout.. Prothrombinase was assembled on phospholipid-coated glass capillaries. Its activity was characterized with respect to the activation of prothrombin (mean plasma concentration, 1.4 μmol/L) in the absence and presence of rivaroxaban (2, 5, and 10 nmol/L). The degree of inactivation of preassembled prothrombinase is sensitive to the solution-phase rivaroxaban concentration; however, prothrombinase unmasking upon removal of rivaroxaban is concentration independent.. The model system presented suggests that when rivaroxaban plasma concentrations decrease after cessation of therapy, there will be an unmasking of thrombus-associated prothrombinase that may be related to the reported rebound phenomena.

Topics: Administration, Oral; Anticoagulants; Blood Flow Velocity; Dose-Response Relationship, Drug; Factor V; Factor Va; Factor Xa; Humans; Models, Biological; Morpholines; Regional Blood Flow; Risk Factors; Rivaroxaban; Thiophenes; Thromboplastin; 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

We report a case of an incidental finding of congenital absence of the intrahepatic segment of the inferior vena cava (IVC) complicated by extensive bilateral deep venous thrombosis (DVT) with significant oedema following a long-distance road trip. Initially the patient failed treatment with standard anticoagulation therapy with enoxaparin and warfarin. However, he has responded to the new oral antifactor-Xa anticoagulant (rivaroxaban). Within a few days, rivaroxaban improved the oedema and DVT. The significant features of this case are the unusual presentation, the poor response to initial standard anticoagulation therapy and the beneficial outcomes when managed with the novel new anticoagulant. The patient has continued the new treatment regularly for the last 12 months with good toleration and without side effects. This report presents the findings, management and outcomes in a case of extensive bilateral DVT in a previously healthy young man who was found to have a congenital short IVC.

Topics: Adult; Anticoagulants; Edema; Enoxaparin; Humans; Iliac Vein; Incidental Findings; Male; Morpholines; Rivaroxaban; Thiophenes; Tomography, X-Ray Computed; Travel; Vena Cava, Inferior; Venous Thrombosis; Warfarin; Young Adult

To analyze the impact of ivaroxaban on hidden blood loss and blood transfusion rate after primary total knee arthroplasty (TKA) by comparing with the use of low molecular weight heparin.. Between December 2009 and January 2011, the clinical data from 90 patients undergoing primary TKA were retrospectively analyzed. At 12 hours after operation, 45 patients were given ivaroxaban (10 mg/d) in the trial group and low molecular weight heparin injection (0.4 mL/d) in the control group for 14 days, respectively. There was no significant difference in gender, age, disease duration, or range of motion between 2 groups (P > 0.05).. The operation time was (92.32 +/- 23.13) minutes in the trial group and (89.81 +/- 18.65) minutes in the control group, showing no significant difference (t=0.26, P=0.79). The hidden blood loss was (40.18 +/- 14.85) g/L in the trial group and (34.04 +/- 12.96) g/L in the control group, showing significant difference (t=2.09, P=0.00); the dominant blood loss was (30.60 +/- 2.89) g/L and (28.85 +/- 8.10) g/L respectively, showing no significant difference (t=1.37, P=0.17). The blood transfusion rate was 73.33% (33/45) in the trial group and 55.56% (25/45) in the control group, showing no sigificant difference (chi2=3.10, P=0.08); the transfusion volume was (1.44 +/- 1.09) U and (1.06 +/- 1.17) U respectively, showing no significant difference (t=1.58, P=0.11). Stress ulcer occurred in 1 case of the trial group; symptomatic deep vein thrombosis of lower extremity and asymptomatic muscular venous thrombosis developed in 1 case and 4 cases of the control group respectively.. Ivaroxaban has effect on the hidden blood loss after primary TKA, which may increase postoperative blood loss and blood transfusion rate. The changes in hemoglobin should be monitored during the anticoagulant therapy, and the blood volume should be added promptly.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Transfusion; Female; Hemoglobins; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Morpholines; Osteoarthritis, Knee; Postoperative Complications; Postoperative Hemorrhage; Range of Motion, Articular; Retrospective Studies; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

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

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Morpholines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thrombosis

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

Topics: Administration, Oral; Anticoagulants; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Dose-Response Relationship, Drug; Factor VIII; Factor Xa Inhibitors; Humans; Morpholines; Netherlands; Partial Thromboplastin Time; Predictive Value of Tests; Prothrombin Time; Rivaroxaban; Thiophenes; Time Factors; Venous Thrombosis

Topics: Acute Disease; Anticoagulants; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

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

Topics: Animals; Anticoagulants; Benzimidazoles; Dabigatran; Disease Models, Animal; Factor Xa Inhibitors; Humans; Mice; Mice, Knockout; Morpholines; Pyridines; Rivaroxaban; Thiophenes; Thrombin; Venous Thrombosis

The anticoagulant and antithrombotic profiles of TAK-442, a direct factor Xa (FXa) inhibitor, were investigated. TAK-442 showed potent inhibition of human FXa (Ki = 1.8 nM) and high specificity, with a 440-fold greater selectivity than thrombin and negligible effects on trypsin, plasmin, and tissue plasminogen activator (K(i) > 30 microM). [corrected] In human plasma, TAK-442 doubled FXa-induced clotting time, prothrombin time (PT), and activated partial thromboplastin time at 0.19, 0.55, and 0.59 microM, respectively. The relative PT-prolonging potencies of TAK-442, rivaroxaban, and apixaban were 1, 2.0-2.6, and 0.46-1.3, respectively, in 4 different PT reagents. In a rabbit model of venous thrombosis, 50- and 100-micrograms/kg [corrected] TAK-442 (intravenous bolus followed by 1-hour infusion) reduced thrombus formation by 50% and 81%, with plasma anti-FXa activity of 23%-26% and 34%-38%, respectively, and only marginal prolongation of PT and activated partial thromboplastin time. Melagatran, a thrombin inhibitor, showed similar antithrombotic activity to TAK-442. However, 500-micrograms/kg [corrected TAK-442 did not affect bleeding time (BT), whereas the same dose of melagatran significantly prolonged BT by 3.6-fold compared with vehicle control. These findings suggest that TAK-442 has similar antithrombotic effects as melagatran but does not cause BT prolongation, and plasma anti-FXa activity may reliably predict its potency.

Topics: Animals; Anticoagulants; Azetidines; Benzylamines; Bleeding Time; Blood Coagulation; Blood Coagulation Tests; Dogs; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Macaca fascicularis; Male; Mice; Mice, Inbred ICR; Morpholines; Pyrazoles; Pyridones; Pyrimidinones; Rabbits; Rats; Rats, Sprague-Dawley; Rivaroxaban; Sulfones; Thiophenes; Thrombin; Venous Thrombosis

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

Apixaban is an oral, direct factor Xa (FXa) inhibitor in late-stage clinical development. This study assessed effects of the direct FXa inhibitors, apixaban and rivaroxaban, vs. the direct thrombin inhibitor, dabigatran, on venous thrombosis (VT), bleeding time (BT) and clotting times in rabbits.. We induced the formation of non-occlusive thrombus in VT models by placing threads in the vena cava, and induced bleeding by the incision of cuticles in anesthetized rabbits. Apixaban, rivaroxaban and dabigatran were infused IV to achieve a stable plasma level. Clotting times, including the activated partial thromboplastin time (aPTT), prothrombin time (PT), modified PT (mPT) and thrombin time (TT), were measured.. Apixaban, rivaroxaban and dabigatran exhibited dose-related efficacy in preventing VT with EC(50) of 65, 33 and 194 nm, respectively. At doses for 80% reduction of control thrombus, apixaban, rivaroxaban and dabigatran prolonged BT by 1.13 +/- 0.02-, 1.9 +/- 0.1-* and 4.4 +/- 0.4-fold*, respectively (*P < 0.05, vs. apixaban). In the treatment model, these inhibitors equally prevented growth of a preformed thrombus. Antithrombotic doses of apixaban and rivaroxaban prolonged aPTT and PT by <3-fold with no effect on TT. Dabigatran was > or = 50-fold more potent in prolonging TT than aPTT and PT. Of the clotting assays studied, apixaban, rivaroxaban and dabigatran responded the best to mPT.. Comparable antithrombotic efficacy was observed between apixaban, rivaroxaban and dabigatran in the prevention and treatment of VT in rabbits. Apixaban and rivaroxaban exhibited lower BT compared with dabigatran at equivalent antithrombotic doses. The clinical significance of these findings remains to be determined.

Topics: Animals; Benzimidazoles; Blood Coagulation Tests; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Morpholines; Pyrazoles; Pyridines; Pyridones; Rabbits; Rivaroxaban; Thiophenes; Thrombin; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Drug Administration Schedule; Enoxaparin; Humans; Morpholines; Research Design; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Knee; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Enoxaparin; Europe; Humans; Morpholines; North America; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Hemorrhage; Humans; Morpholines; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Rivaroxaban; Safety; Thiophenes; Venous Thrombosis

Topics: Anticoagulants; Benzimidazoles; Clinical Trials as Topic; Cost-Benefit Analysis; Dabigatran; Economics, Pharmaceutical; Humans; Morpholines; Pyridines; 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; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Knee; Clinical Trials as Topic; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thrombosis

New oral anticoagulants, soon available in clinical practice, will deeply change the management of venous thromboembolism. The main advantage of these drugs is the route of administration. Moreover, among the new oral anticoagulants, rivaroxaban has a better efficacy than enoxaparin to prevent thromboembolic events after major orthopaedic surgery (THR and TKR). In phase III studies, safety profile seems adequate. A new era for prophylaxis of VTE is beginning with the new oral anticoagulants. However, improvement in the management of patients with renal failure, obese patients or elderly is needed considering that these patients have a high thrombotic and/or hemorrhagic risk.

Topics: Administration, Oral; Aged; Anticoagulants; Clinical Trials, Phase III as Topic; Comorbidity; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Morpholines; Obesity; Postoperative Complications; Preanesthetic Medication; Rivaroxaban; Thiophenes; Thromboembolism; Thrombophilia; Venous Thrombosis

Current anticoagulant therapies for the prevention and treatment of thromboembolic disorders have many drawbacks: vitamin K antagonists interact with food and drugs and require frequent laboratory monitoring, and heparins require parenteral administration. Oral rivaroxaban (BAY 597939) is a new, highly selective and potent direct factor-Xa (FXa) inhibitor with a predictable pharmacodynamic and pharmacokinetic profile and could therefore be an attractive antithrombotic drug. It was the objective of this study to investigate the antithrombotic efficacy of oral rivaroxaban in two rabbit models of experimental venous thrombosis. In the venous stasis (prevention) model, animals were randomized to receive oral rivaroxaban 0.3, 1.0, 3.0 or 10.0 mg/kg or vehicle control. Thrombosis was induced by jugular vein stasis and injection of thromboplastin into the ear vein. In the venous thrombosis (treatment) model, intravenous (1.0 and 3.0 mg/kg) and oral (3.0 mg/kg) rivaroxaban was compared with intravenous nadroparin (40 U bolus and 20 U/h), fondaparinux (42 microg/kg) and vehicle control. Thrombus growth was assessed by measuring the accretion of radiolabelled fibrinogen into preformed clots in the jugular veins. Bleeding was assessed using an ear bleeding model. In the prevention model, rivaroxaban reduced thrombus formation dose-dependently (calculated ED(50) 1.3 mg/kg). In the treatment model, oral rivaroxaban (3.0 mg/kg) reduced thrombus growth to a similar extent to intravenous rivaroxaban (1.0 mg/kg), nadroparin and fondaparinux. Oral rivaroxaban did not prolong bleeding time. In conclusion, the orally available selective, direct FXa inhibitor rivaroxaban is effective in the prevention and treatment of venous thrombosis in two well-established models of experimental thrombosis.

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation Tests; Disease Models, Animal; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Infusions, Intravenous; Injections, Intravenous; Jugular Veins; Ligation; Morpholines; Nadroparin; Polysaccharides; Rabbits; Random Allocation; Rivaroxaban; Thiophenes; Thromboplastin; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dabigatran; Drug Delivery Systems; Drug Design; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Hemorrhage; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Warfarin

BAY 59-7939 is an oral, direct Factor Xa (FXa) inhibitor in development for the prevention and treatment of arterial and venous thrombosis. BAY 59-7939 competitively inhibits human FXa (K(i) 0.4 nm) with > 10 000-fold greater selectivity than for other serine proteases; it also inhibited prothrombinase activity (IC(50) 2.1 nm). BAY 59-7939 inhibited endogenous FXa more potently in human and rabbit plasma (IC(50) 21 nm) than rat plasma (IC(50) 290 nm). It demonstrated anticoagulant effects in human plasma, doubling prothrombin time (PT) and activated partial thromboplastin time at 0.23 and 0.69 microm, respectively. In vivo, BAY 59-7939 reduced venous thrombosis (fibrin-rich, platelet-poor thrombi) dose dependently (ED(50) 0.1 mg kg(-1) i.v.) in a rat venous stasis model. BAY 59-7939 reduced arterial (fibrin- and platelet-rich) thrombus formation in an arteriovenous (AV) shunt in rats (ED(50) 5.0 mg kg(-1) p.o.) and rabbits (ED(50) 0.6 mg kg(-1) p.o.). Slight inhibition of FXa (32% at ED(50)) reduced thrombus formation in the venous model; to affect arterial thrombosis in the rat and rabbit, stronger inhibition of FXa (74%, 92% at ED(50)) was required. Calculated plasma levels in rabbits at the ED(50) were 14-fold lower than in the rat AV shunt model, correlating with the 14-fold lower IC(50) of FXa inhibition in rabbit compared with rat plasma; this may suggest a correlation between FXa inhibition and antithrombotic activity. Bleeding times in rats and rabbits were not significantly affected at antithrombotic doses (3 mg kg(-1) p.o., AV shunt). Based on these results, BAY 59-7939 was selected for clinical development.

Topics: Animals; Blood Coagulation Tests; Disease Models, Animal; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Inhibitory Concentration 50; Morpholines; Rabbits; Rats; Rivaroxaban; Serine Proteinase Inhibitors; Species Specificity; Thiophenes; Thromboplastin; Venous Thrombosis