rivaroxaban and Thrombosis

Direct oral anticoagulants (DOACs) offer an alternative to low-molecular-weight heparin (LMWH) and warfarin for treating cancer-associated thrombosis (CAT).. To determine the cost and effectiveness of DOACs versus LMWH.. Cohort-state transition decision analytic model.. Network meta-analysis comparing DOACs versus LMWH.. Adult patients with cancer at the time they develop thrombosis.. Lifetime.. Health care sector.. Strategies of 1) enoxaparin, 2) apixaban, 3) edoxaban, and 4) rivaroxaban for treatment of CAT.. Incremental cost-effectiveness ratio (ICER) in 2022 U.S. dollars per quality-adjusted life-year (QALY) gained.. In the base-case scenario, using drug prices from the U.S. Department of Veterans Affairs Federal Supply Schedule, apixaban dominated enoxaparin and edoxaban by being less costly and more effective. Rivaroxaban was slightly more effective than apixaban, with an ICER of $493 246. In a scenario analysis using "real-world" drug prices from GoodRx, rivaroxaban was cost-effective with an ICER of $50 053 per QALY.. Results were highly sensitive to monthly drug costs. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of $50 000 per QALY, apixaban was preferred in 80% of simulations. However, sensitivity analyses also demonstrated that apixaban only remained cost-effective if monthly medication costs were below $530. Above this, rivaroxaban became cost-effective.. An assumption was made that patients would continue anticoagulation indefinitely unless they suffered a major bleed. Nonmedical costs such as patient and caregiver loss of productivity were not accounted for, and long-term thrombotic complications were not explicitly modeled.. The 3 DOACs are more effective and more cost-effective than LMWH. The most cost-effective DOAC depends on the relative cost of each of these agents. These are important considerations for treating physicians and health policymakers.. None.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Enoxaparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Quality-Adjusted Life Years; Rivaroxaban; Thrombosis

Transcatheter Aortic Valve Replacement (TAVR) has been established as the treatment of choice for symptomatic aortic stenosis, while it is expanding in all risk-related group categories of patients, gaining gradually ground over the surgical approach. However, complications and adverse events are yet to be effectively limited and diminished with thrombotic and hemorrhagic events being rooted as a crucial topic of discussion. Favorable anticoagulation pharmacotherapy options are constantly being revised and tested, whilst guidelines are being modified to meet current clinical evidence. This review aims to systematically assess already existing guidelines on anticoagulation in post-TAVI patients and examine novel regimens for the specific use, like apixaban, rivaroxaban, and other anticoagulants, essentially constructing a holistic point of view on future progress on this matter. The added complexity brought by coagulation-affecting comorbidities such as atrial fibrillation, coronary artery disease, and more contributes to the direct association of the topic to the quality of healthcare as a public service. The literature was systematically searched to examine the effectiveness and safety of various anticoagulation treatments and cross-evaluate them based on the according category of patients that were assigned to. Clinical trials, observational studies and systematic reviews were included and, eventually, conclusive remarks and future considerations were developed and presented. In the category of patients without prior indication to anticoagulation, SAPT was proven safer and still effective, when antiplatelet therapies were compared, while a comparison of antiplatelet versus anticoagulation strategies noted the first one, with limited data, as the optimal one. Lastly, direct oral anticoagulants were shown to be safe substitutes for vitamin K antagonists for patients with prior indication to anticoagulation.

Topics: Anticoagulants; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome

This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion.. Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

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

Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased risk of thrombotic events. Also, more bleeding events are observed in those who receive anticoagulation compared to those without cancer. In the treatment of cancer-associated thrombosis, direct oral anticoagulants (DOACs) have been found to be at least as effective as low-molecular weight heparins, which became the standard of care after several trials demonstrated superiority over vitamin K antagonists. Non-inferiority compared to low-molecular weight heparins has been shown for rivaroxaban, edoxaban and apixaban with a signal of fewer recurrent thrombotic events, albeit with an increase in bleeding events. Yet, potentially major pharmacokinetic drug-drug interactions have been identified as a reason to withhold DOACs and to rather choose an alternative. Practical guidance on what constitutes a major pharmacokinetic interaction and/or how to deal with these interactions in clinical practice is limited. Hence, here we have provided a framework to allow clinicians to better deal with pharmacokinetic drug-drug interactions between DOACs and cancer therapies in the management of cancer-associated thrombosis. In this review we have discussed the current literature, how the pharmacokinetic profile links to the label information on DDI, and have provided a practical proposal, applied to a clinical case.

Topics: Administration, Oral; Anticoagulants; Drug Interactions; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

Current evidence-based clinical practice guidelines recommend the use of both low-molecular-weight heparin (LMWH) and direct factor Xa inhibitors (apixapan, edoxaban and rivaroxaban) as first-line options for the treatment of venous thromboembolism (VTE) in patients with cancer. However, most of these guidelines refer to the general cancer patient population and provide limited guidance for specific subgroups of patients at particularly high risk of bleeding, such as those with gastrointestinal cancers, primary or metastatic brain tumors, thrombocytopenia, or renal impairment. In these complex populations, the management of cancer-associated thrombosis (CAT) poses unique challenges and requires a nuanced approach based on the primum non nocere principle. This comprehensive review critically examines the relevant literature and discusses the therapeutic options currently available for the management of CAT in these special situations.

Topics: Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

Left atrial appendage closure (LAAC) are emerging treatment for patients with atrial fibrillation (AF). However, data on the safety, efficacy, and medications for LAAC devices in patients with AF are lacking. We aimed to investigate the incidence of all-cause mortality, stroke, and major bleeding in AF patients with LAAC devices and DOACs. Moreover, we aimed to investigate the incidence rate of device-related thrombus (DRT) and the medications used in the management of AF patients with LAAC devices to gain insights into achieving better outcome. Based on a literature search using PubMed, EMBASE, Cochrane Library, and Web of Science databases between January 2015 and December 2020, eight LAAC device studies that used WATCHMAN and Amulet, and three DOAC studies that used rivaroxaban, with a total of 24,055 AF patients (LAAC devices, n = 2855; DOAC, n = 21,200), were included. A random-effects model was used to incorporate heterogeneity among studies. The pooled incidence of events per person-years were as follows: all-cause mortality, 0.06 (95% confidence interval [CI] 0.02-0.10) for WATCHMAN, 0.04 (95% CI 0.00-0.14) for Amulet, and 0.03 (95% CI 0.01-0.04) for rivaroxaban; stroke; 0.02 (95% CI 0.00-0.04) for WATCHMAN, 0 for Amulet, and 0.01 (95% CI 0.01-0.02) for rivaroxaban; major bleeding, 0.04 (95% CI 0.02-0.06) for WATCHMAN, 0.02 (95% CI 0.00-0.06) for Amulet, and 0.02 (95% CI 0.01-0.03) for rivaroxaban. The incidence rate of DRT was 2.3%, and complications were reported in 9%. The incidence of all-cause mortality, stroke, and major bleeding were similar between LAAC devices and DOACs. The rate of complications was acceptable, and those of DRT were lower than the average incidence reported in previous studies. However, further follow-up is needed. Concomitant anticoagulant and antiplatelet therapies should be further evaluated to find the optimal regimen for AF patients with LAAC devices.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Hemorrhage; Humans; Rivaroxaban; Stroke; Thrombosis; Treatment Outcome

Thrombotic events are an increasing challenge in pediatrics. Standard-of-care anticoagulants for pediatric thrombosis have several disadvantages which could be overcome by using direct oral anticoagulants (DOACs). Until recently, there was not enough evidence from clinical trials to recommend for or against the use of any of the four DOACs in children with thrombosis. In this literature review, we looked at the latest clinical trials in this field. On clinicaltrials.gov, we found 13 current studies with published results. For two of the four DOACs, namely dabigatran and rivaroxaban, we found successful phase III studies which led to the approval for the use in children. The results of these pivotal phase III studies allow to finally recommend rivaroxaban and dabigatran for the prophylaxis and treatment of thrombotic events in children.. Thrombotische Ereignisse stellen in der Kindermedizin eine zunehmende Herausforderung dar. Die Standardantikoagulanzien für pädiatrische Thrombosen haben mehrere Nachteile, die durch den Einsatz direkter oraler Antikoagulanzien (DOACs) überwunden werden könnten. Bis vor kurzem war aber noch nicht ausreichend Evidenz aus klinischen Studien verfügbar, um evidenzbasierte Empfehlungen für den Einsatz einer der vier DOACs bei Kindern mit Thrombosen zu geben. In dieser Literaturübersicht haben wir die neuesten klinischen Studien auf diesem Gebiet untersucht. Auf clinicaltrials.gov fanden wir 13 aktuelle Studien mit veröffentlichten Ergebnissen. Für zwei der vier DOACs, namentlich Dabigatran und Rivaroxaban, fanden wir erfolgreiche Phase-III-Studien, die zur Zulassung für den Einsatz bei Kindern führten. Die Evidenz aus diesen zulassungsrelevanten Phase-III-Studien gestattet es daher jetzt, Rivaroxaban und Dabigatran für die Vorbeugung und Behandlung von thrombotischen Ereignissen bei Kindern zu empfehlen.

Topics: Administration, Oral; Adolescent; Anticoagulants; Child; Dabigatran; Humans; Infant, Newborn; Rivaroxaban; Thrombosis

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious. We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types. A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49-8.93; I2  = 29%, P  = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56-4.42; I2  = 0, P  = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99-10.29; I2  = 0, P  = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences. In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Rivaroxaban; Thrombosis; Venous Thromboembolism; Vitamin K

Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15-25% of all VTE cases. For decades, the standard treatment for CAT used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score ≥2 prior to starting new chemotherapy, low bleeding risk, no interfering medications).

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

Limited data are available for the comparison between different non-vitamin K antagonist oral anticoagulants (NOACs) on clinical outcomes. We aimed to provide evidence of different NOACs for patients with non-valvular atrial fibrillation (NVAF).. Electronic databases were searched from inception through 22 March 2020 to identify eligible studies in which clinical outcomes (stroke, systemic embolism [SE], bleeding or death events) were directly compared between different NOACs.. 29 real-world studies enrolled more than 700,000 patients were included. Compared with dabigatran, apixaban had higher risk of death (OR 1.07), major bleeding (1.43), GI bleeding (1.64), ischaemic stroke and stroke/SE events (1.10); rivaroxaban had higher risk of death (1.28), major bleeding (1.24), GI bleeding (1.14) and ischaemic stroke (1.08). Compared with rivaroxaban, apixaban had lower risk of death (0.8), major bleeding (0.56) and ischaemic stroke events (0.71). Compared with edoxaban, rivaroxaban had higher risk of major bleeding (2.83), GI bleeding (5.18) and ischaemic stroke (2.28).. In view of the global burden of disease and the routine use of NOACs worldwide, the findings have immediate and important implications. Our data suggested that apixaban might be the priority choice in prevention of bleeding and stroke and dabigatran could be the priority choice in prevention of death events.. This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews (PRISMA), Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and was registered with PROSPERO (CRD42019140553).

Topics: Anticoagulants; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Ischemic Stroke; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis

Topics: Administration, Oral; Factor Xa Inhibitors; Heart Diseases; Heart Ventricles; Humans; Rivaroxaban; Thrombolytic Therapy; Thrombosis; Treatment Outcome

Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer. Moreover, management of VTE is frequently connected with complications, namely risk of recurrent VTE and bleeding. Low molecular weight heparins (LMWH) therapy administrated for 3-6 months is currently considered a standard for the treatment of cancer-associated VTE (CA-VTE). Direct oral factor Xa inhibitors (FXaI) apixaban, edoxaban and rivaroxaban have emerged as a new possibility for long-term antithrombotic therapy for VTE. These agents expose several advantages in individuals with cancer, and might overcome several disadvantages connected with LMWH therapy.. First clinical studies with oral FXaI for the treatment of CA-VTE with very promising results were recently published. The article summarizes current data regarding the use of oral FXaI in the treatment of CA-VTE.

Topics: Administration, Oral; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Venous Thromboembolism

Nonvitamin K oral anticoagulants (NOACs) or direct oral anticoagulants comprise inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban) or factor IIa (dabigatran). Both classes efficiently interfere with the final or penultimate step of the coagulation cascade and showed superior net clinical benefit compared with vitamin K antagonists for prevention of thromboembolic events in patients with AF and for prevention and therapy of deep vein thrombosis and pulmonary embolism. None the less, accumulating data suggested, that there may be differences regarding the frequency of atherothrombotic cardiovascular events between NOACs. Thus, the optimal individualized NOAC for each patient remains a matter of debate. Against this background, some basic and translational analyses emphasized NOAC effects that impact on platelet activity and arterial thrombus formation beyond inhibition of plasmatic coagulation. In this review, we will provide an overview of the available clinical and translational evidence for so-called noncanonical NOAC effects on platelet activation and arterial thrombosis.

Topics: Animals; Blood Coagulation; Dabigatran; Factor Xa Inhibitors; Humans; Platelet Activation; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis

To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients.. A literature search was conducted for studies evaluating VTE and bleeding outcomes with DOAC use in CKD and dialysis patients. Searches conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from inception to September 22, 2020.. Randomized controlled trials, cohort studies, and case series with ≥10 patients included.. From 7286 studies, nine studies met inclusion criteria. There was no significant difference between DOACs (dabigatran, rivaroxaban, apixaban) and warfarin for reducing recurrent VTE and bleeding events in moderate CKD patients. The risk of overall major bleeding increased when the degree of kidney impairment increased. There was no significant difference between apixaban and warfarin for VTE outcomes in dialysis patients.. There continues to be a controversial debate whether it may be more beneficial to use DOACs versus warfarin in CKD/dialysis patients with venous thromboembolism (VTE). The risk vs benefit of using DOACs in the CKD/ESKD population should continue to be evaluated for each individual patient.. Apixaban may be used cautiously as an alternative in acute VTE treatment in severe CKD patients. Insufficient evidence is available to suggest the use of dabigatran and rivaroxaban in this patient population. The benefit of using DOACs in this population for VTE treatment should be weighed against the potential bleeding risk in patients with CKD.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Thrombosis; Venous Thromboembolism

Topics: Anticoagulants; Antithrombins; Dabigatran; Embolism; Factor Xa Inhibitors; Heart Diseases; Heart Ventricles; Hemorrhage; Humans; Odds Ratio; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Warfarin

Rivaroxaban is a factor Xa inhibitor oral anticoagulant first approved for use in the United States in 2011. Under the drug class commonly termed direct oral anticoagulants, rivaroxaban is approved for the most indications within its class, 7 indications, which are: (1) reduction of risk of stroke and systemic embolism (SE) in nonvalvular atrial fibrillation, (2) treatment of deep vein thrombosis (DVT), (3) treatment of pulmonary embolism (PE), (4) reduction in the risk of recurrence of DVT and/or PE, (5) prophylaxis of DVT following hip or knee replacement surgery, (6) prophylaxis of venous thromboembolism in acutely ill medical patients at risk for thromboembolic complications not at high risk of bleeding, and (7) reduction of risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Considering the relationship between cardiovascular disease, renal impairment, and the use of oral anticoagulants, the following targeted review was created. This review reports the results of the primary pharmacology, pharmacokinetic modeling, clinical safety and efficacy, and real-world postmarketing effectiveness and safety of rivaroxaban in patients with various degrees of renal impairment. Based on these data, rivaroxaban is a viable option for when anticoagulation is needed in patients who have both cardiovascular disease and renal impairment. However, as with any therapy, the benefits and risks of intervention should be carefully assessed and balanced. Patients treated with rivaroxaban for several of its approved indications should have their kidney function assessed prior to and during continued therapy to ensure consistency with the drug label.

Topics: Anticoagulants; Area Under Curve; Humans; Myocardial Infarction; Patient Acuity; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Renal Insufficiency; Rivaroxaban; Stroke; Thrombosis

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

Topics: Anticoagulants; Aspirin; Blood Coagulation; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombolytic Therapy; Thrombosis

: Despite substantial progress in the treatment of atherosclerotic disease a non-negligible rate of acute atherothrombotic events persists. Evidence suggesting a safer profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists and the involvement of coagulation in the atherosclerotic process has led to exploration of the role of DOACs in the prevention of atherothrombotic events. In this review, we discuss the findings of recent studies on DOACs, particularly rivaroxaban, in atherothrombotic disease which represents a new clinical setting for oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Coronary Artery Disease; Humans; Peripheral Arterial Disease; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome

Direct oral anticoagulants, anti-IIa or anti-Xa, are widely used in the treatment and prevention of venous thromboembolic disease as well as in nonvalvular atrial fibrillation. Direct oral anticoagulants are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, theoretical drug interactions exist since direct oral anticoagulants are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway. Direct oral anticoagulants do not have a marketing authorization for the treatment of cancer-associated thrombosis unlike low-molecular-weight heparins which remain the gold standard treatment today. However, recent studies have compared low-molecular-weight heparins to direct oral anticoagulants in the treatment of cancer-associated thrombosis. Results of these studies showed a non-inferiority of direct oral anticoagulants in the prevention of recurrent thromboembolic events but at the cost of an increased hemorrhagic risk, in particular for patients with gastrointestinal and urogenital cancers. Thus, international guidelines, unlike French guidelines, integrate them in first line of the therapeutic strategy of cancer patients. We are certainly entering an era of personalized therapy for cancer-associated thrombosis, considering cancer type and also the theoretical risk of drug interactions with anti-cancer treatments or supportive care.

Topics: Anticoagulants; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Cytochrome P-450 Enzyme System; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasm Proteins; Neoplasms; Pyrazoles; Pyridines; Pyridones; Recurrence; Rivaroxaban; Secondary Prevention; Thiazoles; Thrombosis; Venous Thromboembolism

The off-label use of direct oral anticoagulants (DOACs) for the treatment of left ventricular thrombi has grown over the past several years given the ease of administration, absence of a requirement for international normalized ratio (INR) monitoring, and freedom from dietary restrictions; however, the evidence for their safety and efficacy is contradictory. We systematically searched PubMed and Google Scholar from January 1, 2009, to April 25, 2020, for studies of DOACs for treatment of left ventricular thrombi. Fifty-three articles (of 1,168 patients) met our inclusion criteria. We found that the studies have reached conflicting results; based on our findings, their routine use for the treatment of left ventricular thrombi cannot be recommended. Adequately powered randomized controlled trials are needed to determine the safest and most effective treatment for left ventricular thrombi.

Topics: Dabigatran; Factor Xa Inhibitors; Heart Diseases; Heart Ventricles; Humans; Off-Label Use; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Treatment Outcome

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Topics: Anticoagulants; Cardiology; Cardiovascular Diseases; COVID-19; COVID-19 Drug Treatment; Europe; Heparin, Low-Molecular-Weight; Humans; Inflammation; Practice Guidelines as Topic; Risk Factors; Rivaroxaban; SARS-CoV-2; Societies, Medical; Thrombophilia; 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

The review is devoted to the issue of optimal duration of anticoagulant therapy for venous thromboembolic complications (VTEC) using oral anticoagulants (OAC). These drugs are characterized by higher safety in comparison with vitamin K antagonists and make it possible to increase the duration of treatment for not only spontaneous thrombosis (with high risk of recurrence), but also thrombosis provoked by minor persistent and transient risk factors of VTEC. Efficacy and safety of prolonged treatment of VTEC using OAC was analyzed. Different classifications of primary thrombotic episode depending on risk of subsequent recurrence are presented. Moreover, scales for individual assessment of risk of recurrent thrombosis after anticoagulant therapy cancellation and risk of bleeding in case of continued treatment are given. Outcomes of long-term administration of rivaroxaban for VTEC are analyzed. It was concluded that OAC are safe for prolonged management of primary thrombotic episode. However, overall duration of treatment should be determined considering individual balance of benefits and risks.. Статья представляет собой классический обзор литературы, посвященный вопросам определения оптимальной длительности антикоагулянтной терапии венозных тромбоэмболических осложнений (ВТЭО) в свете широкого внедрения прямых оральных антикоагулянтов (ПОАК). Последние, обладая в сравнении с антагонистами витамина K улучшенным профилем безопасности, позволяют увеличивать длительность лечения не только клинически неспровоцированных тромбозов (наиболее опасных в отношении рецидива), но и спровоцированных малыми персистирующими и транзиторными факторами риска ВТЭО, характеризующихся меньшей угрозой. Проведен анализ результатов исследований по изучению эффективности и безопасности продленной терапии ВТЭО с помощью ПОАК. Представлены различные классификации первичного тромботического эпизода в зависимости от его влияния на риск рецидива, приведены шкалы для индивидуальной оценки угрозы повторного тромбоза после отмены антикоагулянта и опасности кровотечения при продолжении лечения. Проанализированы результаты длительного применения ривароксабана при спровоцированных ВТЭО. Сделан вывод, что применение ПОАК позволяет безопасно увеличивать продолжительность терапии первичного эпизода, однако общая длительность лечения должна быть основана на индивидуальном балансе пользы и риска.

Topics: Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Humans; Recurrence; Risk Factors; Rivaroxaban; Thrombosis; Time Factors; Venous Thromboembolism; Withholding Treatment

While trials have demonstrated non-inferiority of direct oral anticoagulant drugs (DOAC) to low-molecular-weight heparins (LMWH) for the treatment of cancer associated thrombosis (CAT), it is unclear if the newer intervention is cost-effective.. We performed a cost-utility analysis using a Markov state-transition model over a time horizon of 60 months in a hypothetical cohort of 65-year-old patients with active malignancy and first acute symptomatic CAT who were eligible to receive either rivaroxaban/edoxaban or dalteparin. We obtained transition probability, relative risk, cost, and utility inputs from the literature. We estimated the differential impact on costs and quality-adjusted life years (QALYs) per patient and performed one-way and probabilistic sensitivity analyses to test the robustness of results.. Using the base-case analysis over 60 months, DOAC versus dalteparin was associated with an incremental cost reduction of $24,129 with an incremental QALY reduction of 0.04. In the one-way sensitivity analysis, the cost of dalteparin contributed the most to the incremental cost difference; relative risk of death related to underlying cancer contributed the most of the incremental QALY difference. The probabilistic sensitivity analysis confirmed the base-case analysis, with a large reduction in cost but small reduction in QALYs.. Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.

Topics: Anticoagulants; Cost-Benefit Analysis; Dalteparin; Factor Xa Inhibitors; Humans; Neoplasms; Pyridines; Quality-Adjusted Life Years; Rivaroxaban; Thiazoles; Thrombosis

Because atrial fibrillation (AF) is a major risk for thrombotic disease, many patients with AF are managed with anticoagulation for primary or secondary prevention of these events. The emergence of novel oral anticoagulants offers patients and providers options to consider beyond warfarin. Decision making should address safety, tolerability, efficacy, price, and simplicity of use; and decisions should be individualized for each patient.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Thrombosis

Left ventricular (LV) thrombus is commonly seen in patients with extensive anterior ST-elevation myocardial infarction. The standard of care for LV thrombus is anticoagulation with warfarin. However, there has been an increasing trend of case reports using non-vitamin K antagonist oral anticoagulants (NOAC) for the treatment of LV thrombus. This study aimed to perform a meta-summary of the literature to characterise and evaluate the safety and feasibility of using NOAC in patients with LV thrombus. We searched for articles published in four electronic databases: PubMed, EMBASE, Scopus and Google Scholar using an appropriate keyword/MeSH term search strategy. Twenty-four studies comprising 36 patients were included in the analysis. Rivaroxaban was used in majority of patients (47.2%), whilst Apixaban and Dabigatran were prescribed in 25.0% and 27.8% of patients respectively. The most commonly associated risk factor found was post-acute myocardial infarction in 15 patients (41.7%). LV thrombus resolution was met by most patients (87.9%), and the median duration of treatment to resolution was 30.0 days (IQR = 22.5-47.0). One non-fatal bleeding event (3.0%) and no embolic events were reported. The use of NOAC may have a role in the treatment of LV thrombus in selected patients. Further randomized controlled trials are needed to evaluate this treatment strategy.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Myocardial Infarction; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Ventricular Dysfunction, Left

Topics: Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Disease; DNA; Drug Therapy, Combination; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Histones; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis; Warfarin

The prevention of atherothrombotic events is an essential therapeutic goal in the treatment of patients with arteriosclerotic diseases. After plaque rupture, a rapidly growing thrombus can lead to acute vascular occlusion and thus heart attack, stroke or limb ischaemia. The acute therapy combines anticoagulation and platelet inhibition. However, the only available therapy so far in the primary and secondary prevention of stable patients is the platelet inhibitors aspirin and clopidogrel. Despite the use of antiplatelet therapies, including aspirin and P2Y. Die Verhinderung atherothrombotischer Ereignisse ist ein wesentliches therapeutisches Ziel bei der Behandlung von Patienten mit arteriosklerotischen Erkrankungen. Ein schnell wachsender Thrombus kann nach Plaqueruptur zu akutem Gefäßverschluss und damit zu Herzinfarkt, Schlaganfall oder Ischämie der Extremitäten führen. Die Akuttherapie kombiniert Antikoagulation und Thrombozytenhemmung. Die bislang einzige verfügbare Therapie in der Primär- und Sekundärprävention stabiler Patienten sind jedoch die Thrombozytenaggregationshemmer Aspirin und Clopidogrel. Trotz der Verwendung von Thrombozytenaggregationshemmern, einschließlich Aspirin und P2Y12-Rezeptorantagonisten, leiden einige Patienten mit Arterienerkrankungen weiterhin unter kardiovaskulären ischämischen Ereignissen, die auf eine übermäßige Thrombinbildung nach der akuten Phase zurückzuführen sind. Als ein Ergebnis haben Studien Nicht-Vitamin-K-Antagonist-orale Antikoagulantien (NOAKs) getestet, insbesondere die Faktor-Xa-Inhibitoren, entweder allein oder in Kombination mit einer Antiplättchen-Therapie bei der Behandlung von arteriellen Erkrankungen. Die COMPASS-Studie untersuchte erstmals die niedrig dosierte Antikoagulation bei stabiler koronarer Herzkrankheit oder peripherer arterieller Verschlusskrankheit. Die Zugabe von 2 × 2,5 mg Rivaroxaban zur Langzeit-Aspirintherapie verhinderte nicht nur kardiovaskulären Tod, Myokardinfarkt und Schlaganfall, sondern reduzierte sogar die Gesamtmortalität um 18% nach einer mittleren Nachbeobachtungszeit von 23 Monaten. Dieser Vorteil ging auf Kosten von mehr gastrointestinalen Blutungen, die durch die Zugabe eines Protonenpumpenhemmers reduziert werden könnten (Untersuchungen laufen noch). Interessanterweise gab es jedoch keine Zunahme von tödlichen oder intrakraniellen Blutungen. Daher könnte in naher Zukunft eine neue Standardtherapie für Hochrisikopatienten mit atherosklerotischer Erkrankung verfügbar werden.

Topics: Animals; Anticoagulants; Atherosclerosis; Coronary Disease; Heart Failure; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis

The health implications of obesity are myriad and multifaceted. Physiologic changes associated with obesity can affect the absorption, distribution, metabolism, and excretion of administered drugs, thereby altering their pharmacologic profiles. In 2016, the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis published recommendations about the use of direct oral anticoagulants (DOACs) in obese patients. This guidance provides uniform recommendations for all DOACs, yet data suggest that individual agents may be affected to different degrees by obesity. Moreover, there are no recommendations currently available to guide DOAC use in bariatric surgery patients, in whom anatomic and physiologic changes to the digestive system can influence drug pharmacokinetics. Our review of the available literature indicates that the clinical profile of the DOAC rivaroxaban is not affected by high weight or bariatric surgery; hence, it does not appear that rivaroxaban dosing needs to be altered in these patient populations.

Topics: Bariatric Surgery; Factor Xa Inhibitors; Humans; Obesity, Morbid; Practice Guidelines as Topic; Rivaroxaban; Thrombosis

We present the case of a patient with primary APS who had a recurrence of thrombotic event while on treatment with rivaroxaban and had to be restarted on warfarin. The current literature on recurrence of thrombotic events in patients with antiphospholipid syndrome (APS) treated with newer oral anticoagulants (NOAC) is also reviewed. Relevant case reports and case series were identified by searching the Medline database using the key words antiphospholipid syndrome, anticoagulants and names of the NOACs, and data on individual patients was abstracted. We identified several reports on the failure of newer anticoagulants in APS, as well as cases and clinical trial results reporting efficacy. We conclude that treatment strategies for APS should be tailored cautiously when using NOACs.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Middle Aged; Rivaroxaban; Thrombosis; Warfarin

Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)] are at high risk of bleeding events (both non-major and major clinically relevant bleeding). While anticoagulation reduces the risk of thromboembolic events, the co-existing bleeding risk and the fact that the most commonly used anticoagulation agents are eliminated via the kidneys pose additional challenges. More recently, two classes of direct oral anticoagulant agents (DOACs) have been investigated for the prevention and management of venous thromboembolic events: the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin inhibitor dabigatran. In this review, we discuss the complex challenges and the practical considerations associated with the management of anticoagulation treatment in patients with CKD, with a special focus on DOACs.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Heparin; Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Rivaroxaban; Thrombosis; Vitamin K

The anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity, associated with a persistent positivity for anti-phospholipid antibodies (aPL). The current classification criteria for APS include three laboratory tests: lupus anti-coagulant (LA), anti-cardiolipin (aCL), and anti-β2 glycoprotein-I (β2GPI). To date, the therapeutic approach for thrombotic APS mainly centers on long-term anti-coagulation with a vitamin K antagonist (VKA). APS management may represent a challenge for the treating physicians. Patients with different aPL profiles need a tailored risk-stratified approach. Moreover, in patients with recurrent thrombotic events despite therapy with VKA, or in those with microvascular involvement, new therapeutic options are highly needed. In this review, we aim to elucidate recent findings about new aPL specifities, available risk scoring models, and novel therapeutic approaches in APS management.

Topics: Adult; Antibodies, Anticardiolipin; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Female; Fibrinolytic Agents; Humans; Hydroxychloroquine; Lupus Coagulation Inhibitor; Pregnancy; Pregnancy Complications; Risk Assessment; Rivaroxaban; Thrombosis

The phase III non-vitamin K dependent oral anticoagulants (NOAC) studies and recently published real world data on the use of dabigatran and rivaroxaban have shown that the bleeding profile in particular of intracranial and other life-threatening bleeding of NOAC is more favourable than that of warfarin. In case of a bleeding complication in a patient treated with a NOAC the recently updated EHRA practical guide offers management strategies. Idarucizumab, the specific antidot for dabigatran is approved to reverse the anticoagulant effect of dabigatran-treated patients who have serious bleeding and require an urgent procedure. Andexanet alfa, a specific antidot for direct and indirect factor Xa-inhibitors will be available in the future. The frequency of thrombocytopenia in ICU patients is high whereas the heparin induced thrombocytopenia (HIT) only counts for a small minority of patients with thrombocytopenia. To avoid an overdiagnosis of HIT a reliable and complete clinical and laboratory workup has to be performed. New immunoassays have been developed to provide results within a short period of time. These tests appear to have improved diagnostic accuracy compared with ELISAs in patients with suspected HIT and may reduce misdiagnosis and overtreatment. Acquired haemophilia (AH) is a rare and often life threatening bleeding disorder caused by autoantibodies against factor VIII. Susoctocog alfa is a B-domain deleted recombinant factor VIII porcine sequence that has recently been approved to treat severe bleeding in patients with AH. Susoctocog alfa offers the ability to effectively titrate and monitor dosing based on factor VIII activity levels.

Topics: Anticoagulants; Dabigatran; Hemophilia A; Hemorrhage; Heparin; Humans; Intensive Care Units; Rivaroxaban; Thrombocytopenia; Thrombosis; Warfarin

The cornerstone of thrombotic antiphospholipid syndrome (APS) patients' management is to prevent recurrent thrombosis by long-term anticoagulation.. The purpose of the review is to summarize available literature on direct oral anticoagulants (DOACs) use in APS patients through a systematic review and to determine factors associated with thrombosis recurrence.. The recent RAPS trial demonstrated that APS patients treated with rivaroxaban had a significant twofold-increased thrombin potential, suggesting a higher thrombotic risk, in comparison with warfarin users. Furthermore, several reports of APS patients treated with DOACs have raised safety issues. Our systematic review identified 122 published APS patients treated with DOACs; among them, 19 experienced a recurrent thrombosis while on DOACs. Of note, triple positivity (positivity of all three laboratory criteria for APS) was associated with a 3.5-fold increased risk for recurrent thrombosis. In conclusion, DOACs should be used with caution in APS patients and randomized control trials with clinical primary endpoints assessing clinical efficacy and safety are awaited to establish whether the prescription of DOACs could be a safe alternative to warfarin.

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Secondary Prevention; Thrombosis; Warfarin

Data on nonvitamin K antagonist oral anticoagulant being used for the treatment of LAA thrombi are limited only in nonvalvular atrial fibrillation. There are no data on the antithrombotic efficacy and safety of nonvitamin K antagonist oral anticoagulant in the resolution of left atrial appendage (LAA) thrombi in patients with rheumatic mitral stenosis.. A 49-year-old woman with known rheumatic mitral stenosis and atrial fibrillation was referred for percutaneous transvenous mitral commissurotomy because of progressive dyspnea on exertion over a period of 3 months.. Transesophageal echocardiography (TEE) demonstrated a large LAA thrombus protruding into left atria cavity before the procedure.. Direct factor Xa (FXa) inhibitor rivaroxaban (20 mg/d) was started for the patient. After 3 weeks of rivaroxaban treatment TEE showed a relevantly decreased thrombus size, and a complete thrombus resolution was achieved after 5 weeks of anticoagulant therapy with the FXa inhibitor.. To the best of our knowledge, this is the first documented case of large LAA thrombus resolution with nonvitamin K antagonist oral anticoagulant in severe mitral stenosis, and in which percutaneous transvenous mitral commissurotomy was performed subsequently.. The report indicated that rivaroxaban could be a therapeutic option for mitral stenosis patients with LAA thrombus. Further study is required before the routine use of rivaroxaban in patients with rheumatic mitral stenosis and atrial fibrillation.

Topics: Atrial Appendage; Cardiac Surgical Procedures; Female; Follow-Up Studies; Humans; Middle Aged; Minimally Invasive Surgical Procedures; Mitral Valve Stenosis; Preoperative Care; Risk Assessment; Rivaroxaban; Severity of Illness Index; Thrombosis; Treatment Outcome

Several new anticoagulants have entered the clinical arena or are under clinical development. These drugs include indirect (fondaparinux) and direct oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban), and the direct thrombin inhibitor dabigatran. Especially the oral direct FXa and FIIa inhibitors overcome many of the shortcomings of heparins and vitamin K antagonists (VKAs). They are administered orally at a fixed dose; regular monitoring is not necessary; interaction with other drugs or nutrition occur less than with VKAs and they are at least as effective as VKAs for most indications tested. They are associated with about 50 % less intracranial bleeding than VKAs. Nevertheless, they are still associated with bleeding complications. Bleeding can occur spontaneously or as a result of trauma or urgent surgery. In such situations rapid reversal of the anticoagulant effect is highly desirable. For unfractionated heparin protamine, and for VKAs prothrombin complex concentrates are available as specific antidotes. Under clinical development are: for the direct and indirect FXa inhibitors a modified recombinant FXa (andexanet alpha), which lacks enzymatic activity; and for dabigatran a Fab fragment of a monoclonal antibody (idarucizumab). In addition a small molecule (aripazine) has entered phase I clinical trials, which seems to inhibit nearly all anticoagulants but VKAs and argatroban. This review summarises the current options and strategies in development to antagonise anticoagulants with a focus on the status of the development of antidotes for the oral direct FXa and FIIa inhibitors.

Topics: Administration, Oral; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antithrombins; Benzamides; Clinical Trials as Topic; Dabigatran; Factor Xa; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Hemostatics; Heparin; Humans; Infusions, Parenteral; Intracranial Hemorrhages; Polysaccharides; Protamines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiazoles; Thrombosis; Vitamin K

The novel oral anticoagulants (NOAC) dabigatran, apixaban, edoxaban and rivaroxaban target either thrombin or factor Xa for the prevention and treatment of thrombosis. A short introduction of the main indications for an oral anticoagulation is followed by the pharmacology of each drug, their effectiveness, selected drug-drug interactions and adverse drug events, especially bleeding. The article represents clinical aspects for the perioperative management, the possibilities for monitoring of each drug, the application in patients with renal impairment as well as different advantages and disadvantages.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Perioperative Care; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis

Regarding anticoagulant therapies there has been a remarkable shift in recent years. The objective of this brief overview is to provide relevant information and guidelines on the advantages and disadvantages of novel anticoagulants addressing specifically the surgical disciplines. Hitherto, conventional anticoagulant therapy in patients with a high thrombosis risk was largely limited to heparins and vitamin-K antagonists (VKA). Their modes of action, the difficulties in managing VKAs (e.g., bridging therapy) and the risk of HIT (heparin-induced thrombocytopenia) associated with heparins are briefly discussed. Novel anticoagulants supposedly eliminate these obstacles. Fondaparinux (Arixtra®) is a fully synthetic pentasaccharide which acts like a heparin but has an increased half life. Fondaparinux has a diminished risk of HIT. However, no specific antidote is currently available for Fondaparinux. The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa®), rivaroxaban (Xarelto®) and apixaban (Eliquis®), also known as "direct" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. In addition, interactions with other medication may have unexpected effects on serum drug levels. Therefore, the analysis of drug levels in the plasma may become necessary in subgroups of patients.. Studies establishing clear recommendations for the desirable and measurable reference range are needed. Similarly, evidence-based recommendations regarding perioperative prevention of thrombosis are required ("bridging": yes or no?). Irrespective of these issues, the authors predict a further expansion of the use of NOACs.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Blood Coagulation Tests; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; International Normalized Ratio; Liver Failure; Metabolic Clearance Rate; Morpholines; Perioperative Care; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis; Vitamin K

The best regimen for the long-term management of patients with atrial fibrillation who present with an acute coronary syndrome or require placement of a coronary stent remains unclear. Clinicians need to understand the risk of stroke, stent thrombosis, and major bleeding associated with treating these patients. Numerous studies and risk assessment schemes provide clinicians with an estimation of the risk of stroke, stent thrombosis, and major bleeding that may be associated with the use or avoidance of dual antiplatelet therapy with concurrent anticoagulation therapy (triple therapy). This review discusses the special antithrombotic needs in patients who have atrial fibrillation and either acute coronary syndrome or a requirement for percutaneous coronary intervention, including the published evidence for non-vitamin K oral anticoagulants, and the unanswered questions in this patient population. In conclusion, until the results of additional ongoing or planned randomized trials are known, clinicians must continue to rely on expert opinion and their own clinical judgment when treating these patients.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Comorbidity; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Morpholines; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis; Ticagrelor

Heparins and vitamin K antagonists (VKA) used commonly are the standard treatment of venous and arterial thromboses. They are very efficient and safe, but have some limitations: iatrogenicity, laboratory monitoring, parenteral use for heparins and fondaparinux. Nowadays, four new inhibitors of factor Xa are used orally (rivaroxaban, apixaban, edoxaban, betrixaban), and they are at least as efficient as heparins and vitamin K antagonists. The objective is to substitute these indirect inhibitors of factor Xa (heparins, low molecular weight heparins and fondaparinux) in the prevention of venous and arterial thromboembolic episodes. The new direct inhibitors do not require routine laboratory monitoring of blood coagulation. They inhibit the extrinsic and the intrinsic pathways of blood coagulation. Rivaroxaban and apixaban are efficacious and safe in the prevention of cerebral infarcts in patients with non-valvular fibrillation. Apixaban is another direct inhibitor of factor Xa used orally which is developed in the same indications as rivaroxaban. Edoxaban and betrixaban are also in development. The objective of this work is to study the pharmacodynamic, pharmacokinetic, the efficacy and safety of these four oral direct factor Xa inhibitors.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Benzamides; Blood Coagulation; Embolism; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombophilia; Thrombosis

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Embolism; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K; Warfarin

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

Disadvantages with traditional anticoagulants (vitamin K antagonists and heparinoids) have led to the development on non-vitamin K antagonist oral anticoagulants (NOACs). These agents are set to replace the traditional anticoagulants in situations such as following orthopaedic surgery, in atrial fibrillation, and in the prevention and treatment of venous thromboembolism. Although superior to vitamin K antagonists and heparinoids in several aspects, NOACs retain the ability to cause haemorrhage and, despite claims to the contrary, may need monitoring. This review aims to summarise key aspects of the NOACs of relevance to the laboratory.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Dose-Response Relationship, Drug; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Thrombosis; Treatment Outcome; Vitamin K

The use of new oral anticoagulants (NOACs) is expected to rise significantly in upcoming years. Therefore, it is important to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages over warfarin, including a rapid onset and offset of action, fewer drug interactions, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their ease of administration and the advantage of eliminating the requirement for regular coagulation monitoring. NOACs work to prevent and treat thrombosis by targeting either thrombin (as with dabigatran) or factor Xa (as with rivaroxaban and apixaban). In this review, we discuss practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Dabigatran; Drug Interactions; Humans; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis

Until recently, it was widely accepted that patients with cirrhosis have a bleeding tendency related to the changes in the hemostatic system that occur as a consequence of the disease. However, it has now been well established that patients with cirrhosis are at risk for both bleeding and thrombotic complications. These thrombotic complications include portal vein thrombosis, deep vein thrombosis and pulmonary embolism, and coronary or cerebrovascular infarctions. Antithrombotic drugs to prevent or treat thrombotic complications in patients with cirrhosis have been used only minimally in the past due to the perceived bleeding risk. As the thrombotic complications and the necessity of antithrombotic treatment in these patients are increasingly recognized, the use of antithrombotic drugs in this population is likely increasing. Moreover, given the rising incidence of fatty liver disease and generally longer survival times of patients with chronic liver diseases, it would be reasonable to presume that some of these thrombotic complications may be increasing in incidence over time. In this review, we will outline the indications for antithrombotic treatment in patients with cirrhosis. Furthermore, we will discuss the available antithrombotic drugs and indicate possible applications, advantages, and caveats. Since for many of these drugs very little experience in patients with cirrhosis exists, these data are essential in the design of future clinical and laboratory studies on mechanisms, efficacy, and safety of the various antithrombotic strategies in these patients.

Topics: Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Disease Progression; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Liver Cirrhosis; Morpholines; Platelet Aggregation Inhibitors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

The introduction of several oral direct anticoagulants within the past 2-3 years has dramatically changed clinical practice and has also impacted on utilization and interpretation of coagulation laboratory testing. This article reviews the effects of the oral thrombin inhibitor, dabigatran, and the oral factor Xa inhibitors, rivaroxaban and apixaban, on screening and diagnostic coagulation tests, and describes methods for measuring the their anticoagulant activity in plasma. Currently, there are evidence gaps regarding the role of laboratory testing for surveillance and management of adverse events associated with these new anticoagulants which do not require routine therapeutic drug monitoring. This is a rapidly changing field, and coagulation laboratory experts have a major role in ensuring patients receive appropriate testing and accurate interpretations of results.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation; Blood Coagulation Tests; Dabigatran; Humans; Morpholines; Outcome Assessment, Health Care; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis

The development of rivaroxaban (XARELTO®) is an important new medical advance in the field of oral anticoagulation. Thrombosis-mediated conditions constitute a major burden for patients, healthcare systems, and society. For more than 60 years, the prevention and treatment of these conditions have been dominated by oral vitamin K antagonists (such as warfarin) and the injectable heparins. Thrombosis can lead to several conditions, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and/or death. Prevention and treatment of thrombosis with an effective, convenient-to-use oral anticoagulant with a favorable safety profile is critical, especially in an aging society in which the risk of thrombosis, and the potential for bleeding complications, is increasing. Rivaroxaban acts to prevent and treat thrombosis by potently inhibiting coagulation Factor Xa in the blood. Factor Xa converts prothrombin to thrombin, which initiates the formation of blood clots by converting fibrinogen to clot-forming fibrin and leads to platelet activation. After a large and novel clinical development program in over 75,000 patients to date, rivaroxaban has received approval for multiple indications in the United States, European Union, and other countries worldwide to prevent and treat several thrombosis-mediated conditions. This review will highlight some of the unique aspects of the rivaroxaban development program.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Treatment Outcome

Novel oral anticoagulants, direct thrombin inhibitors, and factor Xa inhibitors are being introduced into clinical practice. In contrast to vitamin K antagonists, such as warfarin, these novel agents, because of their relatively wide therapeutic range and predictable pharmacokinetics, have been evaluated in clinical trials and approved for clinical use without the need for routine coagulation monitoring. On occasion, it will be important to assess the anticoagulant status of patients treated with these agents. As a result of their targeted mechanisms of action, they affect standard coagulation assays differently than vitamin K antagonists and heparins, and such assay results may not provide clinically useful information. Thus, less commonly used coagulation assays (eg, chromogenic anti-factor Xa activity assays, diluted thrombin time, and ecarin-based clotting tests) may be introduced into clinical practice. These assays are currently limited by the absence of validated therapeutic targets and lack of standardization across laboratories, vendors, and medication classes. This article provides an overview of the coagulation assays and their potential role in determining the anticoagulant status of patients treated with the emerging anticoagulants.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Dabigatran; Drug Monitoring; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Thrombosis

The eighth edition (AT8) of the American College of Chest Physicians (ACCP) Antithrombotic Therapy and Prevention of Thrombosis Guideline, published in June 2008, was a comprehensive presentation of primary studies and detailed discussions of rationale for recommendations. This resulted in an approximately 900-page Chest Supplement publication. Updating the guidelines in a succinct fashion posed a formidable challenge for the ninth edition (AT9), published in February 2012. The strategy adopted for AT9 was to publish an Executive Summary of the recommendations in a 50-page document in the Chest supplement highlighting the changes, with online publication of the full version. Major innovative changes include a recognition of the value of estimating the risk reductions in symptomatic, as opposed to asymptomatic (venographically), detected venous thrombosis, using nonconflicted methodologists as topic editors, new insights into evidence, and increasing emphasis on what is known about patients' values and preferences that have served to improve this edition of the guidelines. This review provides a summary of the updates of the guidelines for anticoagulation therapy and prevention of thrombosis. The AT9 recommendations are presented with, if included, the AT8 recommendations in parenthesis for comparison purposes.

Topics: Drug Synergism; Fibrinolytic Agents; Humans; Morpholines; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Thrombosis; United States; Vitamin K

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Dosage Calculations; Drug Interactions; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombosis; Vitamin K; Warfarin

The new oral anticoagulants are approved for a variety of clinical syndromes, including the prevention of stroke in atrial fibrillation, acute coronary syndromes, treatment of venous thromboembolism (VTE), and prevention of venous thrombosis after total joint surgery or hip fracture. Published guidelines have differing recommendations on the safe interval between discontinuation of the anticoagulant and performance of neuraxial procedures and between the interventional procedure and redosing of the drug. While two to three half-life intervals might be acceptable in patients who are at high risk for VTE or stroke, an interval of four to six half-lives between discontinuation of the drug and neuraxial injections is probably safer in most patients at low risk of thrombosis. In those with renal disease, the interval should be based on creatinine clearance. After a neuraxial procedure or removal of an epidural catheter, anticoagulants can be resumed within 24-48 h in most patients, but they can be taken sooner in patients who are at higher risk for VTE or stroke, that is, 24 h minus the time to peak effect of the drug. The new antiplatelet drugs prasugrel and ticagrelor should be stopped 7 or 5 days, respectively, before a neuraxial injection and can be restarted 24 h later. In selected situations, laboratory monitoring of the anticoagulant effect is appropriate, and reversal agents are suggested when there is a need to rapidly restore haemostatic function.

Topics: Administration, Oral; Anesthesia, Conduction; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis

The new oral anticoagulants are now a reality and are available to clinicians. Although a large number of patients have been included in the many clinical trials of these drugs, there is one population that is always underrepresented - called special populations - such as those aged more than 75 years old, the obese, and patients with renal impairment. This review aims to analyze differences in the efficacy and safety in these special populations recruited in the various trials.

Topics: Administration, Oral; Age Factors; Anticoagulants; Benzimidazoles; Contraindications; Dabigatran; Embolism; Humans; Morpholines; Obesity; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Rivaroxaban; Stroke; Thiophenes; Thrombosis

Direct experimental safety comparisons of Xa coagulation factor direct inhibitors, apixaban and rivaroxaban, on their approved therapeutic indications have not been identified. Due to recently raised safety concerns, a meta-analysis was carried out pooling data from studies identified on a Medline and Cochrane Library search in order to better evaluate the safety profile of both drugs. Abstracts from scientific meetings were also searched from 2003 to 2011. Primary and secondary outcome measures were major bleeding and total bleeding, respectively. Relative risks (RRs) were estimated using random effects models and statistical heterogeneity was estimated with I(2) statistics. Of the 160 screened publications, 12 clinical trials were included in which enoxaparin was the active control. For knee arthroplasty, apixaban was associated with significantly fewer major bleeding events (6496 patients, RR 0.56, 95% confidence interval [CI] 0.32-0.96) and fewer total bleeding events (6496 patients, RR 0.81, 95% CI 0.67-0.97). There were no significant differences in the incidence of major bleeding events (5699 patients, RR 1.40, 95% CI 0.56-3.52) or in the incidence of total bleeding events for rivaroxaban (5699 patients, RR 1.09, 95% CI 0.91-1.30). No differences were found when thromboprophylaxis after hip replacement was the case. Apixaban seems to be associated with a lower risk of the incidence of hemorrhagic events after total knee arthroplasty. For hip arthroplasty, no differences were found between the studied drugs.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis

The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management.. We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban. The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal.. There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Evidence-Based Medicine; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Practice Guidelines as Topic; Pyridines; Rivaroxaban; Societies, Medical; Thiophenes; Thrombosis; United States; Vitamin K

After more than 50 years of thrombosis treatment and prophylaxis being based on heparin and vitamin K antagonists, a new generation of oral, direct anticoagulants is now available. The past 5 years have brought a strikingly large number of trials that evaluated these new oral anticoagulants in a range of clinical trials, particularly nonvalvular atrial fibrillation, thrombosis prophylaxis after major joint replacement surgery, treatment of venous thromboembolic events, and, most recently, acute coronary syndrome. These studies have been notably similar in design between the drugs for specific indication. This review focuses on the 3 drugs that either have recently been approved by the US Food and Drug Administration (dabigatran and rivaroxaban) or have the most mature phase III clinical data (apixaban).

Topics: Acute Coronary Syndrome; Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation; Dabigatran; Hemorrhage; Humans; Morpholines; Orthopedic Procedures; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Treatment Outcome

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

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

Patients with acute coronary syndrome (ACS) continue to be at risk for recurrent ischemic events, despite an early invasive strategy and the use of dual antiplatelet therapy. The anticoagulant pathway remains activated for a prolonged period after ACS and, consequently, has been a target for treatment. Early studies with warfarin indicated its benefit, but the risk of bleeding and the complexities of warfarin anticoagulation resulted in little use of this strategy. Rivaroxaban, apixaban, and dabigatran are new specific inhibitors of anticoagulant factors (Xa or IIa) currently available for the prevention of thrombosis and/or thromboembolism. Thus far, studies with dabigatran and apixaban in ACS have shown no clinical benefit and bleeding has been increased. The ATLAS ACS 2-TIMI 51 trial observed the impact of rivaroxaban 2.5 mg and 5 mg twice daily in patients with recent ACS receiving current management (both early invasive strategy and dual antiplatelet therapy with aspirin and clopidogrel) over a follow-up period of over 1 year. Rivaroxaban 2.5 mg twice daily reduced cardiovascular death, myocardial infarction, or stroke by 16%, and both cardiovascular and all-cause mortality by approximately 20%. Although major bleeding increased from 0.6% to 2.1% and intracranial hemorrhage from 0.2% to 0.6%, there was no increase in fatal bleeding. The role of rivaroxaban in the management of ACS is discussed in this review. The reduction in mortality is the main finding that could lead to the use of rivaroxaban in the management of ACS in high-risk individuals with a low bleeding risk.

Topics: Acute Coronary Syndrome; Anticoagulants; Dose-Response Relationship, Drug; Hemorrhage; Humans; Intracranial Hemorrhages; Morpholines; Risk; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis; Warfarin

Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient's risk for thromboembolic events balanced against the risk for perioperative bleeding. Procedures can be separated into those with a low bleeding risk, which generally do not require complete reversal of the antithrombotic therapy, and those associated with an intermediate or high bleeding risk. For patients who are receiving warfarin who need interruption of the anticoagulant, consideration must be given to whether simply withholding the anticoagulant is the optimal approach or whether a perioperative "bridge" with an alternative agent, typically a low-molecular-weight heparin, should be used. The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Middle Aged; Morpholines; Perioperative Care; Risk; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis; Vitamin K

The new oral anticoagulants are rapidly replacing warfarin for several indications. In contrast to warfarin, which lowers the functional levels of all of the vitamin K-dependent clotting factors, the new agents target either factor Xa or thrombin. With targeted inhibition of coagulation, the new oral anticoagulants have pharmacologic and clinical features that distinguish them from warfarin. Focusing on these features, this paper (a) compares the pharmacology of the new oral anticoagulants with that of warfarin (b) identifies the class effects of these drugs and their differentiating features, (c) reviews their current indications, and (d) uses this information to help clinicians make informed decisions regarding the choice of the right anticoagulant for the right patient.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Chemistry, Pharmaceutical; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Hematology; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombin; Thrombosis; Warfarin

A number of new oral anticoagulant drugs that selectively and directly inhibit factor Xa (FXa) appear as promising alternatives to the existing anticoagulant agents. These compounds present a convenient route of administration with predictable pharmacokinetics and pharmacodynamics that allow fixed dosing regimens without requiring coagulation monitoring. Rivaroxaban is the first of this new class of drugs that was approved for the prevention of venous thromboembolism (VTE) after elective total hip replacement or total knee replacement surgery in the EU, Canada and several other countries. Clinical trials with rivaroxaban in patients with acute VTE and in patients with atrial fibrillation have been recently completed. Numerous other compounds are under different developing stages (apixaban, edoxaban, otamixaban, LY517717, PRT-054021, YM150).. This review provides an overview of the two oral anti-FXa drugs at the most advanced stage of development (rivaroxaban and apixaban) and briefly describes and comments on the results of the most important studies.. Undoubtedly, these new drugs will offer several advantages over the previous compounds, but a number of issues still require some attention during the phase of translation from clinical trials into daily clinical practice.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Drugs, Investigational; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Venous Thromboembolism

Conventional anticoagulants have proven efficacy in the management of thromboembolism. Their adverse effects and a narrow therapeutic window, necessitating regular need for monitoring, however, have long been an incentive for the development of safer anticoagulants without compromising efficacy. Over the last decade or so several new parenteral and oral anticoagulants have been launched with efficacy comparable with conventional agents. From fondaparinux to its long acting derivative idraparinux, and the factor Xa inhibitor rivaroxaban to the direct thrombin inhibitor dabigatran, the advent of new anticoagulants is radically changing anticoagulation. For conventional anticoagulants, despite their shortcomings, effective methods of reversing their anticoagulant effects exist. Moreover, strategies to deal with the occurrence of fresh thrombotic events in the face of therapeutic anticoagulation with the conventional agents have also been addressed. Nevertheless, for the new anticoagulants, the optimal management of these complications remains unknown. This review explores these issues in the light of current evidence.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis; Treatment Failure

Topics: Administration, Oral; Animals; Anticoagulants; Biological Availability; Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; Factor Xa Inhibitors; Hemostasis; Humans; Models, Molecular; Protein Conformation; Structure-Activity Relationship; Thrombosis

Cancer-associated thrombosis is a major cause of morbidity and mortality. Although anticoagulation remains the mainstay for prevention and treatment of thrombosis, current anticoagulants are problematic in cancer patients. Parenteral anticoagulants, such as heparin or low-molecular heparin, require daily subcutaneous injection, whereas warfarin requires coagulation monitoring and frequent dose adjustments. Idrabiotaparinux, a reversible long-acting pentasaccharide, and new oral anticoagulants, such as dabigatran etexilate, rivaroxaban and apixaban, have been designed to replace warfarin for extended prevention or treatment of VTE. Clinical trials with these agents have yielded promising results, and dabigatran etexilate and rivaroxaban are already licensed in many countries for thromboprophylaxis after elective hip or knee replacement surgery. In the coming years, these drugs are likely to replace warfarin for most indications. This paper addresses their potential role for prevention and treatment of cancer-related thrombosis.

Topics: Anticoagulants; Benzimidazoles; Biotin; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Neoplasms; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombosis

Warfarin is commonly used in a number of clinical settings. Given the difficulties in managing patients taking warfarin, several questions are usually raised by clinicians in relation to its use.. This article addresses some of the clinical questions related to warfarin use.. Routine genetic testing before warfarin initiation is not currently recommended. None of the new oral anticoagulants is marketed in Australia for long term therapy as warfarin substitutes. Strategies to prevent thrombosis associated with air travel are discussed and measures to minimise the risk of bleeding are highlighted.

Topics: Anticoagulants; Aspirin; Benzimidazoles; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; International Normalized Ratio; Morpholines; Pharmacogenetics; Pyridines; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Venous Thromboembolism

Prevention and treatment of thrombosis represent some of the most common medical interventions in the clinical area that remains among the most common causes of mortality and morbidity. At present, heparins, pentasaccharides and warfarin are used to prevent thromboembolic events. Nevertheless, these drugs have a range of adverse effects and other disadvantages that force scientists to seek new treatment options that would fulfil the concept of an 'ideal antithrombotic drug'. Characteristics of such an agent include selectivity of its effect, absence of adverse effects, possibility to administer the drug without the need for laboratory control and low cost. Attention is, therefore, focused on thrombin modulation either with direct inhibitors or with inhibitors of the thrombin production system, i.e. activated factor Xa of the plasma coagulation cascade (F Xa). Management so far involved injectable formulations, the efforts described above aim for oral administration of treatment.

Topics: Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis

Topics: Angioplasty, Balloon, Coronary; Angiotensin II Type 2 Receptor Blockers; Anticoagulants; Atrial Fibrillation; Cardiology; Coronary Disease; Drug-Eluting Stents; Heart Diseases; Humans; Morpholines; Myocardial Infarction; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Current anticoagulant provision is dominated by parenteral low-molecular-weight heparin and oral vitamin K antagonists (VKAs), which indirectly inhibit several steps of the coagulation pathway. Two unmet needs for anticoagulation are safety and ease of use. Safety relates primarily to the incidence of major bleeding, which remains the key concern of orthopaedic surgeons and anaesthetists, over and above any efficacy advantage, and convenience of use, which centres on oral administration replacing the need for injections or monitoring platelets or coagulation with VKA. Recent research efforts towards identifying small-molecule inhibitors of coagulation enzymes as novel therapies for thrombotic disorders have been particularly successful in developing orally available molecules to directly inhibit the key proteases, factors IIa and Xa. Of the new oral anticoagulants in development, dabigatran etexilate (BIBR 1048) and rivaroxaban (BAY 59-7939), which inhibit factors IIa and Xa, respectively, are the most advanced and were approved in Europe in 2008. Based on the available data, we can conclude that dabigatran etexilate is non-inferior to enoxaparin in terms of efficacy and safety, and two different doses (220 and 150 mg/day) have now been approved. The 150 mg/day dose is intended for elderly patients and those with moderate renal impairment, which allows clinicians to decrease the risk of bleeding in the increasing number of fragile patients undergoing major orthopaedic surgery. In conclusion, rivaroxaban is superior in efficacy to enoxaparin, even with the US enoxaparin dosing regimen (30 mg b.i.d.), without significant differences in safety.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morpholines; Orthopedic Procedures; Prothrombin; Pyridines; Risk Assessment; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Topics: Animals; Factor Xa Inhibitors; Heart Diseases; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis

Indirect systemic and direct oral factor Xa and direct oral factor IIa inhibitors with improved pharmacologic profiles compared with heparins and vitamin K antagonists are currently in clinical development. This overview focuses on the indirect antithrombin dependent pentasaccharide derivatives of idraparinux and on the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran). Specifically, the results of dose-finding studies for the prevention of venous thromboembolism after elective orthopedic surgery, the results of dose-finding studies for treatment of acute venous thromboembolism including prolonged prophylaxis of recurrent events, and the designs of ongoing clinical trials are reviewed.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzimidazoles; Benzylamines; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Glycine; Humans; Infusions, Parenteral; Morpholines; Oligosaccharides; Piperazines; Prothrombin; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombin; Thrombosis; Venous Thromboembolism

Rivaroxaban is a small molecule, direct Factor Xa inhibitor and may be a potentially attractive alternative to vitamin K antagonists. Rivaroxaban is being investigated for the prevention and treatment of venous and arterial thrombosis. A broad search of Medline, clinicaltrials.gov and the annual proceedings of the American Society of Hematology and the International Society on Thrombosis and Hemostasis was conducted. This review addresses the findings of this systematic search, including the need for new oral anticoagulants, the development and pharmacology of rivaroxaban, and the results of completed as well as ongoing trials with rivaroxaban. 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. Additionally, rivaroxaban is 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 drug may have its greatest impact in providing a much-needed and attractive alternative to warfarin. Further data (especially large Phase III trials) are required.

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Aged, 80 and over; Animals; Anticoagulants; Atrial Fibrillation; Binding Sites; Clinical Trials as Topic; Comorbidity; Drug Evaluation, Preclinical; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Rats; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Warfarin

Topics: Angina, Unstable; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Brain Ischemia; Clinical Trials as Topic; Coumarins; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Forecasting; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Morpholines; Myocardial Infarction; Peptide Fragments; Polysaccharides; Prothrombin; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Thrombosis; Warfarin

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

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

Andexanet alfa is a modified recombinant inactive factor Xa (FXa) designed to reverse FXa inhibitors. ANNEXA-4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) was a multicenter, prospective, phase-3b/4, single-group cohort study that evaluated andexanet alfa in patients with acute major bleeding. The results of the final analyses are presented.. Patients with acute major bleeding within 18 hours of FXa inhibitor administration were enrolled. Co-primary end points were anti-FXa activity change from baseline during andexanet alfa treatment and excellent or good hemostatic efficacy, defined by a scale used in previous reversal studies, at 12 hours. The efficacy population included patients with baseline anti-FXa activity levels above predefined thresholds (≥75 ng/mL for apixaban and rivaroxaban, ≥40 ng/mL for edoxaban, and ≥0.25 IU/mL for enoxaparin; reported in the same units used for calibrators) who were adjudicated as meeting major bleeding criteria (modified International Society on Thrombosis and Haemostasis definition). The safety population included all patients. Major bleeding criteria, hemostatic efficacy, thrombotic events (stratified by occurring before or after restart of either prophylactic [ie, a lower dose, for prevention rather than treatment] or full-dose oral anticoagulation), and deaths were assessed by an independent adjudication committee. Median endogenous thrombin potential at baseline and across the follow-up period was a secondary outcome.. There were 479 patients enrolled (mean age, 78 years; 54% male; 86% White); 81% were anticoagulated for atrial fibrillation, and the median time was 11.4 hours since last dose, with 245 (51%) on apixaban, 176 (37%) on rivaroxaban, 36 (8%) on edoxaban, and 22 (5%) on enoxaparin. Bleeding was predominantly intracranial (n=331 [69%]) or gastrointestinal (n=109 [23%]). In evaluable apixaban patients (n=172), median anti-FXa activity decreased from 146.9 ng/mL to 10.0 ng/mL (reduction, 93% [95% CI, 94-93]); in rivaroxaban patients (n=132), it decreased from 214.6 ng/mL to 10.8 ng/mL (94% [95% CI, 95-93]); in edoxaban patients (n=28), it decreased from 121.1 ng/mL to 24.4 ng/mL (71% [95% CI, 82-65); and in enoxaparin patients (n=17), it decreased from 0.48 IU/mL to 0.11 IU/mL (75% [95% CI, 79-67]). Excellent or good hemostasis occurred in 274 of 342 evaluable patients (80% [95% CI, 75-84]). In the safety population, thrombotic events occurred in 50 (10%) patients; in 16 patients, these occurred during treatment with prophylactic anticoagulation that began after the bleeding event. No thrombotic episodes occurred after oral anticoagulation restart. Specific to certain populations, reduction of anti-FXa activity from baseline to nadir significantly predicted hemostatic efficacy in patients with intracranial hemorrhage (area under the receiver operating characteristic curve, 0.62 [95% CI, 0.54-0.70]) and correlated with lower mortality in patients <75 years of age (adjusted. In patients with major bleeding associated with the use of FXa inhibitors, treatment with andexanet alfa reduced anti-FXa activity and was associated with good or excellent hemostatic efficacy in 80% of patients.. URL: https://www.. gov; Unique identifier: NCT02329327.

Topics: Aged; Anticoagulants; Cohort Studies; Enoxaparin; Factor Xa; Factor Xa Inhibitors; Female; Hemorrhage; Hemostatics; Humans; Male; Prospective Studies; Recombinant Proteins; Rivaroxaban; Thrombin; Thrombosis

Evidence on the treatment for left ventricular (LV) thrombus is limited and mainly derives from retrospective studies. The aim of R-DISSOLVE was to explore the effectiveness and safety of rivaroxaban in patients with LV thrombus. R-DISSOLVE was a prospective, interventional, single-arm study, conducted from Oct 2020 to June 2022 at Fuwai Hospital, China. Patients with a history of LV thrombus < 3 months and with systemic anticoagulation therapy < 1 month were included. The thrombus was quantitatively confirmed by contrast-enhanced echocardiography (CE) at baseline and follow-up visits. Eligible patients were assigned to rivaroxaban (20 mg once daily or 15 mg if creatinine clearance was between 30 and 49 mL/min) and its concentration was determined by detecting anti-Xa activity. The primary efficacy outcome was the rate of LV thrombus resolution at 12 weeks. The main safety outcome was the composite of ISTH major and clinically relevant non-major bleeding. A total of 64 patients with complete CE results were analyzed for efficacy outcomes. The mean LV ejection fraction was 25.4 ± 9.0%. The dose-response curve of rivaroxaban was satisfactory based on the peak and trough plasma levels and all concentrations were in the recommended treatment range according to NOAC guidelines. The incidence rate of thrombus resolution at 6 weeks was 66.1% (41/62, 95% CI 53.0-77.7%), and of thrombus resolution or reduction was 95.2% (59/62, 95% CI 86.5-99.0%). At 12 weeks, the thrombus resolution rate was 78.1% (50/64, 95% CI 66.0-87.5%) while the rate of thrombus resolution or reduction was 95.3% (61/64, 95% CI 86.9-99.0%). The main safety outcome occurred in 4 of 75 patients (5.3%) (2 ISTH major bleeding and 2 clinically relevant non-major bleeding). In patients with LV thrombus, we reported a high thrombus resolution rate with acceptable safety by rivaroxaban, which could be a potential option for further LV thrombus treatment.Trial registration This study was registered at ClinicalTrials.gov as NCT04970381.

Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Prospective Studies; Retrospective Studies; Rivaroxaban; Thrombosis; Treatment Outcome

COVID-19 (coronavirus disease 2019) is associated with heightened risks of venous and arterial thrombosis and hospitalization due to respiratory failure. To assess whether prophylactic anticoagulation can safely reduce the frequency of venous and arterial thrombosis, hospitalization, and death in nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor, we conducted the PREVENT-HD double-blind, placebo-controlled randomized trial (A Study of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19] Infection).. PREVENT-HD was conducted between August 2020 and April 2022 at 14 US integrated health care delivery networks. A virtual trial design used remote informed consent and clinical monitoring and facilitated data collection through electronic health record integration with a cloud-based research platform. Nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor were enrolled and randomly assigned to either 10 mg of oral rivaroxaban or placebo daily for 35 days. The primary efficacy outcome was time to first occurrence of a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic arterial embolism, hospitalization, or death through day 35. The principal safety end point was International Society on Thrombosis and Hemostasis critical-site or fatal bleeding. The last study visit was on day 49.. The study was terminated prematurely because of enrollment challenges and a lower-than-expected blinded pooled event rate. A total of 1284 patients underwent randomization with complete accrual of primary events through May 2022. No patients were lost to follow-up. The primary efficacy outcome occurred in 22 of 641 in the rivaroxaban group and 19 of 643 in the placebo group (3.4% versus 3.0%; hazard ratio, 1.16 [95% CI, 0.63-2.15];. The study was terminated prematurely after enrollment of 32% of planned accrual because of recruitment challenges and lower-than-expected event rate. Rivaroxaban prescribed for 35 days in nonhospitalized patients with symptomatic COVID-19 at risk for thrombosis did not appear to reduce a composite end point of venous and arterial thrombotic events, hospitalization, and death.. URL: https://www.. gov; Unique identifier: NCT04508023.

Topics: Anticoagulants; COVID-19; Hemorrhage; Hospitalization; Humans; Outpatients; Rivaroxaban; Thrombosis

Abdominal aortic aneurysm (AAA) is a fatal disease due to the tendency to rupture. The drug treatment for small AAA without surgical indications has been controversial. Previous studies showed that high-sensitivity C-reactive protein (hs-CRP) had become a potential biomarker of the disease, and the anti-inflammatory effect of rivaroxaban for AAA had been well established. Thus, we hypothesized that rivaroxaban could control the progression of AAA in patients with hs-CRP elevation.. The study is a prospective, open-label, randomized, controlled clinical trial. Sixty subjects are recruited from the General Hospital of Northern Theatre Command of China. Subjects are randomly assigned (1:1) to the intervention arm (rivaroxaban) or control arm (aspirin). The primary efficacy outcome is the level of serum hs-CRP at 6 months. The secondary outcomes include imaging examination (the maximal diameter of AAA, the maximal thickness of mural thrombus, and the length of aneurysm), major adverse cardiovascular and cerebrovascular events (MACCE, including AAA transformation, non-fatal myocardial infarction, acute congestive heart failure, stent thrombosis, ischemia-driven target vessel revascularization, vascular amputation, stroke, cardiovascular death, and all-cause death), and other laboratory tests (troponin T, interleukin 6, D-dimer, and coagulation function).. The BANBOO trial tested the effect of rivaroxaban on the progression of AAA in patients with elevated Hs-CRP for the first time.. ChiCTR2100051990, ClinicalTrials.gov, registered on 12 October 2021.

Topics: Aortic Aneurysm, Abdominal; Aspirin; C-Reactive Protein; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Thrombosis; Treatment Outcome

Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI.. APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power.. The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone.. gov Identifier: NCT05077683.

Topics: Anterior Wall Myocardial Infarction; Anticoagulants; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome

Thrombosis remains an important complication for children with single-ventricle physiology following the Fontan procedure, and effective thromboprophylaxis is an important unmet medical need. To obviate conventional dose-finding studies and expedite clinical development, a rivaroxaban dose regimen for this indication was determined using a model-informed drug development approach. A physiologically based pharmacokinetic rivaroxaban model was used to predict a pediatric dosing regimen that would produce drug exposures similar to that of 10 mg once daily in adults. This regimen was used in an open-label, multicenter phase III study, which investigated the use of rivaroxaban for thromboprophylaxis in post-Fontan patients 2 to 8 years of age. The pharmacokinetics (PK) of rivaroxaban was assessed in part A (n = 12) and in part B (n = 64) of the UNIVERSE study. The safety and efficacy in the rivaroxaban group were compared to those in the acetylsalicylic acid group for 12 months. Pharmacodynamic end points were assessed in both parts of the study. Rivaroxaban exposures achieved in parts A and B were similar to the adult reference exposures. Prothrombin time also showed similarity to the adult reference. Exposure-response analysis did not identify a quantitative relationship between rivaroxaban exposures and efficacy/safety outcomes within the observed exposure ranges. A body weight-based dose regimen selected by physiologically based pharmacokinetic modeling was shown in the UNIVERSE study to be appropriate for thromboprophylaxis in the post-Fontan pediatric population. Model-based dose selection can support pediatric drug development and bridge adult dose data to pediatrics, thereby obviating the need for dose-finding studies in pediatric programs.

Topics: Anticoagulants; Area Under Curve; Body Weights and Measures; Child; Child, Preschool; Female; Fontan Procedure; Humans; Male; Models, Biological; Partial Thromboplastin Time; Prospective Studies; Prothrombin Time; Rivaroxaban; Thrombosis

Vascular disease burden after lower extremity revascularization (LER) comprises more than the first event, more vascular beds than the local arteries, and more than one clinical event type.. Assess total arterial and venous thrombotic burden after LER for symptomatic peripheral artery disease (PAD) and effect of low-dose anticoagulation added to low-dose antiplatelet therapy.. VOYAGER PAD randomized 6564 symptomatic PAD patients undergoing LER to rivaroxaban 2.5 mg twice-daily or placebo on aspirin background. Marginal proportional-hazards models used to generate treatment hazard ratios and associated 95% CIs for first and total events; non-thrombotic deaths treated as competing terminal events. Incidence rates calculated as number of events per 100 patient-years follow-up.. Over 2.5 years (median), first and total thrombotic event rates: 7.1 and 10.3 events/100 patient-years, respectively, in placebo group. Two-thirds (925/1372) of total thrombotic events (arterial 95%, venous 5%) were nonfatal first events. Nearly one-third of patients with first event had a second arterial or venous thrombotic event. Rivaroxaban plus aspirin reduced first and total arterial and venous thrombotic events to 5.4 and 7.9 events/100 patient-years, respectively, a reduction in total thrombotic events over aspirin of 23% (HR: 0.77, 95%CI: 0.67-0.89, p = .0005), preventing 6.1 total arterial and venous thrombotic events at 3 years.. Assessing total arterial and venous thrombotic events, not just first events, provides more complete information about disease burden and absolute on-treatment impact. Following LER, judicious modulation of more than one coagulation pathway can provide broader benefit than intensifying inhibition of one hemostatic system component.

Topics: Anticoagulants; Arteries; Aspirin; Endovascular Procedures; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis

The aim of this study was to investigate the effects of rivaroxaban on left ventricle thromboprophylaxis in patients with anterior ST-segment elevation myocardial infarction (STEMI).. Anterior STEMI is associated with an increased risk of left ventricular thrombus (LVT) formation. The contemporary role of prophylactic rivaroxaban therapy remains unclear.. We randomly assigned 279 patients with anterior STEMI who had undergone primary percutaneous coronary intervention to receive, in a 1:1 ratio, low-dose rivaroxaban (2.5 mg twice daily for 30 days) and dual antiplatelet therapy (DAPT) or only DAPT. The primary efficacy outcome was the LVT formation within 30 days. Net clinical adverse events were assessed at 30 days and 180 days, including all-cause mortality, LVT, systemic embolism, rehospitalization for cardiovascular events, and bleeding.. The addition of low-dose rivaroxaban to DAPT reduced LVT formation within 30 days compared with only DAPT (0.7% vs 8.6%; HR: 0.08; 95% CI: 0.01-0.62; P = 0.015; P < 0.001 for superiority). Net clinical adverse events were lower within 30 days in the rivaroxaban group versus those in the only DAPT group and remained relatively low throughout the follow-up period. There were no significant differences in bleeding events between the 2 groups in 30 days and 180 days. However, 1 case of intracranial hemorrhage (major bleeding) occurred in the rivaroxaban group within 30 days.. Our results supported that the short-duration addition of low-dose rivaroxaban to DAPT could prevent LVT formation in patients with anterior STEMI following primary percutaneous coronary intervention. A larger multiple-institution study is necessary to determine the generalizability.

Topics: Dual Anti-Platelet Therapy; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome

Appropriate regimens of antithrombotic therapy for patients with atrial fibrillation (AF) and coronary artery disease (CAD) have not yet been established.. To compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and combined rivaroxaban and antiplatelet therapy in such patients.. This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label, randomized clinical trial. This multicenter analysis was conducted from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. Data were analyzed from September 1, 2020, to March 26, 2021.. Rivaroxaban monotherapy or combined rivaroxaban and antiplatelet therapy.. The total incidence of thrombotic, bleeding, and fatal events was compared between the groups. Cox regression analyses were used to estimate the risk of subsequent events in the 2 groups, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable.. A total of 2215 patients (mean [SD] age, 74 [8.2] years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis. The total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108), respectively, during a median follow-up of 24.1 (IQR, 17.3-31.5) months. The mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group. Rivaroxaban monotherapy was associated with a lower risk of total events compared with combination therapy (hazard ratio, 0.62; 95% CI, 0.48-0.80; P < .001). Monotherapy was an independent factor associated with a lower risk of subsequent events compared with combination therapy. The mortality risk after a bleeding event (monotherapy, 75% [6 of 8]; combination therapy, 62.1% [18 of 29]) was higher than that after a thrombotic event (monotherapy, 25% [2 of 8]; combination therapy, 37.9% [11 of 29]).. Rivaroxaban monotherapy was associated with lower risks of total thrombotic and/or bleeding events than combination therapy in patients with AF and stable CAD. Tapered antithrombotic therapy with a sole anticoagulant should be considered in these patients.. ClinicalTrials.gov Identifier: NCT02642419.

Topics: Aged; Atrial Fibrillation; Coronary Artery Disease; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Rivaroxaban; 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

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

Background Patients with single-ventricle physiology who undergo the Fontan procedure are at risk for thrombotic events associated with significant morbidity and mortality. The UNIVERSE Study evaluated the efficacy and safety of a novel liquid rivaroxaban formulation, using a body weight-adjusted dosing regimen, versus acetylsalicylic acid (ASA) in children post-Fontan. Methods and Results The UNIVERSE Study was a randomized, multicenter, 2-part, open-label study of rivaroxaban, in children who had undergone a Fontan procedure, to evaluate its dosing regimen, safety, and efficacy. Part A was the single-arm part of the study that determined the pharmacokinetics/pharmacodynamics and safety of rivaroxaban in 12 participants before proceeding to part B, whereby 100 participants were randomized 2:1 to open-label rivaroxaban versus ASA. The study period was 12 months. A total of 112 participants were enrolled across 35 sites in 10 countries. In part B, for safety outcomes, major bleeding occurred in one participant on rivaroxaban (epistaxis that required transfusion). Clinically relevant nonmajor bleeding occurred in 6% of participants on rivaroxaban versus 9% on ASA. Trivial bleeding occurred in 33% of participants on rivaroxaban versus 35% on ASA. For efficacy outcomes, 1 participant on rivaroxaban in part B had a pulmonary embolism (2% overall event rate); and for ASA, 1 participant had ischemic stroke and 2 had venous thrombosis (9% overall event rate). Conclusions In this study, participants who received rivaroxaban for thromboprophylaxis had a similar safety profile and fewer thrombotic events, albeit not statistically significant, compared with those in the ASA group. Registration URL: https://www.clinicaltrials.gov. Identifier: NCT02846532.

Topics: Anticoagulants; Aspirin; Child; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Stroke; Thrombosis; Venous Thromboembolism

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Topics: Administration, Oral; Aspirin; Atrial Fibrillation; Atrial Flutter; Bioprosthesis; Brazil; Cause of Death; Creatinine; Embolism; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Mitral Valve; Rivaroxaban; Sample Size; Stroke; Surgical Procedures, Operative; Thrombosis; Treatment Outcome; Warfarin

COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established.. PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events.. PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

Topics: Adult; Cause of Death; COVID-19; Double-Blind Method; Extremities; Factor Xa Inhibitors; Female; Hemorrhage; Hospital Mortality; Hospitalization; Humans; Ischemia; Ischemic Stroke; Male; Middle Aged; Myocardial Infarction; Outpatients; Placebos; Rivaroxaban; Thrombosis; Venous Thromboembolism

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

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

Observational studies have suggested a higher risk of thrombotic events in patients with coronavirus disease 2019 (COVID-19). Moreover, elevated D-dimer levels have been identified as an important prognostic marker in COVID-19 directly associated with disease severity and progression. Prophylactic anticoagulation for hospitalized COVID-19 patients might not be enough to prevent thrombotic events; therefore, therapeutic anticoagulation regimens deserve clinical investigation.. ACTION is an academic-led, pragmatic, multicenter, open-label, randomized, phase IV clinical trial that aims to enroll around 600 patients at 40 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with symptoms up to 14 days and elevated D-dimer levels will be randomized to a strategy of full-dose anticoagulation for 30 days with rivaroxaban 20 mg once daily (or full-dose heparin if oral administration is not feasible) vs standard of care with any approved venous thromboembolism prophylaxis regimen during hospitalization. A confirmation of COVID-19 was mandatory for study entry, based on specific tests used in clinical practice (RT-PCR, antigen test, IgM test) collected before randomization, regardless of in the outpatient setting or not. Randomization will be stratified by clinical stability at presentation. The primary outcome is a hierarchical analysis of mortality, length of hospital stay, or duration of oxygen therapy at the end of 30 days. Secondary outcomes include the World Health Organization's 8-point ordinal scale at 30 days and the following efficacy outcomes: incidence of venous thromboembolism , acute myocardial infarction, stroke, systemic embolism, major adverse limb events, duration of oxygen therapy, disease progression, and biomarkers. The primary safety outcomes are major or clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria.. The ACTION trial will evaluate whether in-hospital therapeutic anticoagulation with rivaroxaban for stable patients, or enoxaparin for unstable patients, followed by rivaroxaban through 30 days compared with standard prophylactic anticoagulation improves clinical outcomes in hospitalized patients with COVID-19 and elevated D-dimer levels.

Topics: Administration, Oral; Anticoagulants; Brazil; COVID-19; Drug Administration Schedule; Enoxaparin; Fibrin Fibrinogen Degradation Products; Hemorrhage; Hospitalization; Humans; Oxygen Inhalation Therapy; Rivaroxaban; Thrombosis; Time Factors

Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y. We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician's discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y. There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y. UMIN000016612; NCT02642419.

Topics: Aged; Aspirin; Atrial Fibrillation; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Humans; Male; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Thrombosis; Treatment Outcome

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Topics: Acute Coronary Syndrome; Clopidogrel; Dose-Response Relationship, Drug; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Female; Fibrinolysis; Humans; Male; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombelastography; Thrombosis; Ticagrelor

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients. Efficacy and safety outcomes in patients with renal impairment in MARINER (7.5 mg once daily) were compared with those in patients with normal renal function in MARINER (10 mg once daily) and in a subpopulation of MAGELLAN that excluded patients at high risk for bleeding at baseline (10 mg once daily). Compared with enoxaparin/placebo in the MAGELLAN subpopulation, the relative risk (RR) of symptomatic venous thromboembolism (VTE) and VTE-related death with rivaroxaban 10 mg in patients with renal impairment (RR = 0.62; 95% confidence interval [CI] 0.27-1.44) was similar to that in those with normal renal function (RR = 0.78; 95% CI 0.44-1.40), while in MARINER, the 7.5 mg dose did not reduce the risk in patients with renal impairment (hazard ratio = 1.00; 95% CI 0.52-1.92). Major bleeding with rivaroxaban 10 mg once daily was higher in patients with renal impairment than in those with normal renal function in MAGELLAN (1.54% vs. 0.98%) and in the MAGELLAN subpopulation (0.94% vs. 0.61%). At a dose of 10 mg once daily, rivaroxaban is effective for thromboprophylaxis in acutely ill medical patients with impaired or normal renal function. The safety of this regimen is enhanced without loss of efficacy by excluding patients at high risk for bleeding, but not by using a reduced-dose strategy. TRIAL REGISTRATION:  ClinicalTrials.gov identifiers: NCT00571649 for the MAGELLAN trial, NCT02111564 for the MARINER trial.

Topics: Acute Disease; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Hemorrhage; Humans; Incidence; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome; Venous Thromboembolism

This prospective, stratified, randomized, single-blind, placebo-controlled multicentre study investigated the safety and effectiveness of reducing blood loss and preventing venous thromboembolism (VTE) during posterior lumbar interbody fusion (PLIF) in patients with stenosis or spondylolisthesis using the combination of tranexamic acid (TXA) and rivaroxaban.. The Autar score was evaluated in patients after admission. Patients with an Autar score ≤ 10 were randomized to group A or B. Group A was the placebo-controlled group. Patients in group B were treated with 1 g TXA via intravenous injection and 1 g TXA for external use. Patients with an Autar score > 10 were randomized to group C or D. Patients in group C were treated with 10-mg rivaroxaban qd for 35 days after surgery. Patients in group D received the same treatment as those in group B intra-operatively and as those in group C post-operatively.. A total of 599 patients from eight hospitals participated in this clinical trial. The total blood loss, intra-operative blood loss, and drainage volume were reduced by the administration of TXA (group A vs group B, P < 0.01; group C vs group D, P < 0.01), and the blood transfusion rate was also decreased (group A vs group B, P < 0.01; group C vs group D, P < 0.01). There were no significant differences (P > 0.05) in the VTE incidence rates among group A and group B. In patients with high-risk thrombosis, the number of patients with VTE was only three and seven after the application of rivaroxaban. Epidural haematoma was not discovered in any patients in our trial.. The combined application of tranexamic acid and rivaroxaban significantly reduced the amount of blood loss and the transfusion rate during PLIF surgery and avoided an increase in the probability of thrombosis and the occurrence of epidural haematoma.. ChiCTR-1800016430 2018-06-01.

Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Humans; Prospective Studies; Rivaroxaban; Single-Blind Method; Thrombosis; Tranexamic Acid; Treatment Outcome

The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.. To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.. 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36).. 6 university hospitals in Spain.. 190 adults (aged 18 to 75 years) with thrombotic APS.. Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis).. The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding.. After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease.. Anticoagulation intensity was not measured in the rivaroxaban group.. Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis.. Bayer Hispania.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vitamin K; Warfarin

Anticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE.. This study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications.. This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals.

Topics: Adult; Aged; Factor Xa Inhibitors; Humans; Middle Aged; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism; Young Adult

Despite dual antiplatelet therapy, persistent thrombin generation and thrombin-mediated platelet activation account in part for the residual risk of atherothrombotic disease among patients with prior acute coronary syndrome (ACS). Inhibition of thrombin generation among high-risk ACS patients (biomarker-positive ACS) with the factor Xa inhibitor rivaroxaban may limit ongoing thrombus formation and myocardial necrosis and thereby improve clinical outcomes.. ATLAS ACS 2-TIMI 51 was a double-blind, placebo-controlled clinical trial that randomized ACS patients to either rivaroxaban 2.5 mg b.i.d., rivaroxaban 5 mg b.i.d., or placebo plus standard-of-care antiplatelet therapy for a mean of 13.1 months and up to 31 months ( N=15,526). This post-hoc analysis evaluates the safety and efficacy of rivaroxaban among biomarker-positive ACS patients with and without a history of prior stroke of transient ischemic attack in the ATLAS ACS 2-TIMI 51 trial.. A total of 12,626 biomarker-positive ACS patients were included in this analysis. Among biomarker-positive patients without a prior history of stroke or transient ischemic attack, rivaroxaban 2.5 b.i.d. was associated with a reduction in the primary efficacy endpoint (composite of cardiovascular death, myocardial infarction, or stroke) as compared with placebo (hazard ratio=0.80, 95% confidence interval (0.68-0.94), p=0.007) at the expense of an increase in non-coronary-artery-bypass-graft-related Thrombolysis in Myocardial Infarction major bleeding (1.9% vs. 0.7%, p<0.0001), but not a significant increase in either intracranial hemorrhage (0.4% vs. 0.2%, p=0.11) or fatal bleeding (0.1% vs. 0.3%, p=0.16).. Rivaroxaban 2.5 mg b.i.d. was associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, or stroke with no increase in fatal bleeding. Biomarker-positive patients with no prior history of stroke or transient ischemic attack may be a optimal target population to receive "dual pathway" therapy with rivaroxaban plus dual antiplatelet therapy for secondary prevention following ACS.

Topics: Acute Coronary Syndrome; Administration, Oral; Biomarkers; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors; Follow-Up Studies; Humans; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention; Thrombolytic Therapy; Thrombosis; Time Factors; Treatment Outcome; Troponin

Autologous adoptive T cell immunotherapy has been recognized as an effective treatment for cancer patients. The initial qualified lymphocytes is the core element determining the immunotherapeutic outcomes clinically. Cell separator based apheresis procedure is an optimal procedure to collect adequate mono-nucleated lymphocytes to generate efficient ex vivo T cell expansions; however, potential catheter-associated femoral vein thrombosis at post-apheresis might rise an additional deteriorated morbidity for cancer patients. The emerging prophylactic medications are required at such circumstances. Therefore this study was designed to compare the prophylactic effects of rivaroxaban versus low molecular weight heparin (LMWH) in patients who had exposed during the femoral vein catheterization for apheresis. 74 Patients were randomized 1:1:1 into three groups: subcutaneous injection of LMWH, Fraxiparine (n = 23) (0.4 ml, 3800 IU/day) for 2 days, oral rivaroxaban 10 mg/d (n = 26), and oral rivaroxaban 20 mg/d (n = 25) for consecutive 2 days. The primary endpoint was to compare the venous thromboembolism (VTE) occurrence cases in one month post catheterization. There were 4 cases confirmed VTE occurrence in LMWH group with contrast to 1 case in rivaroxaban 10 mg administration group. None was seen in rivaroxaban 20 mg group (P = 0.02 as the comparison with LMWH). Meantime there was no bleeding events occurrence afterwards. Oral rivaroxaban 20 mg/day was recommendable to be considered which superior to LMWH. Although these limited data and patient volume reached the statistical difference which was able to provide the evidence proofed to compare the potency of those two anticoagulants, it could be regarded as the preliminary data provide the clinical results for cancer patients who were placed in the condition of apheresis and subsequently undergone adoptive T cell immunotherapy.Trial registration ClinicalTrials.gov identifier, NCT03282643. Registered 16 February 2016, http://www.ClinicalTrials.gov/ NCT03282643.

Topics: Adoptive Transfer; Adult; Aged; Blood Component Removal; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Rivaroxaban; T-Lymphocytes; Thrombosis

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.

Topics: Acenocoumarol; Adult; Anticoagulants; Elasticity; Factor Xa Inhibitors; Female; Fibrin; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Viscosity; Vitamin K; Warfarin

The Fontan procedure is the final step of the 3-stage palliative procedure commonly performed in children with single ventricle physiology. Thrombosis remains an important complication in children after this procedure. To date, guideline recommendations for the type and duration of thromboprophylaxis after Fontan surgery are mainly based on extrapolation of knowledge gained from adults at risk for thrombosis in other clinical settings. Warfarin is being used off-label, and because of its multiple interactions with other drugs and food, a new alternative is highly desirable. Rivaroxaban, a direct Factor Xa inhibitor with a predictable pharmacokinetic profile, is a candidate to address this medical need.. The UNIVERSE study is a prospective, open-label, active-controlled, multicenter study in children 2 to 8 years of age who have single ventricle physiology and had the Fontan procedure within the 4 months preceding enrollment. This study consists of 2 parts. In Part A, rivaroxaban pharmacokinetics, pharmacodynamics, safety, and tolerability are assessed to validate the pediatric dosing selected. In Part B, safety and efficacy of rivaroxaban versus acetylsalicylic acid are evaluated for thromboprophylaxis in children post-Fontan procedure. Children in each part will receive study drug for 12 months. Part A has been completed with 12 children enrolled. Enrollment into Part B is currently ongoing.. The UNIVERSE study aims to provide dosing, pharmacokinetics/pharmacodynamics, safety, and efficacy information on the use of rivaroxaban, an oral anticoagulant, versus acetylsalicylic acid, an antiplatelet agent, in children with single ventricle physiology after the Fontan procedure.

Topics: Aspirin; Child; Child, Preschool; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fontan Procedure; Humans; Male; Multicenter Studies as Topic; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Thrombosis

Data on LA/LAA thrombus resolution after rivaroxaban treatment has not been established. The aim of the present study was to compare the efficacy and safety on the resolution of LA/LAA thrombus between rivaroxaban and warfarin in nonvalvular atrial fibrillation (AF) patients. 80 AF patients with LA/LAA thrombus between January 2013 and June 2016 were randomized divided into warfarin group (n = 40) and rivaroxaban group (n = 40). Compared to warfarin group, thrombin time (TT; p < 0.0001), plasma prothrombin time (PT; p < 0.0001), and activated partial thromboplastin time (APTT; p = 0.0019) were significantly lower, and fibrinogen (FIB; p < 0.0001) was significantly higher in rivaroxaban group. TEE shown the average length (p < 0.0001), average width (p = 0.0008) and average area (p < 0.0001) of thrombus were significantly lower in rivaroxaban group compared to warfarin group after 6-week treatments. No major or fatal bleeding and ischemic stroke occurred in both two groups. The 20 mg dose Rivaroxaban is more effective than warfarin on the resolution of LA/LAA thrombus in nonvalvular AF patients especially after 6-week treatments. The results suggest that rivaroxaban is a potential option for the treatment of LA/LAA thrombus in patients with nonvalvular AF.

Topics: Adult; Aged; Atrial Appendage; Atrial Fibrillation; Blood Coagulation Tests; Female; Fibrinogen; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

Non-vitamin K antagonist oral anticoagulants including rivaroxaban are widely used for stroke prevention in patients with atrial fibrillation (AF). We investigated the relationship between plasma biomarkers (indicative of thrombogenesis, fibrinolysis and inflammation) and left atrial thrombus resolution after rivaroxaban treatment.. This was an ancillary analysis of the X-TRA study, which was a prospective interventional study evaluating the use of rivaroxaban for left atrial/left atrial appendage (LA/LAA) thrombus resolution in AF patients. We assessed various biomarkers of thrombogenesis/fibrinolysis [D-dimer, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1 + 2 (F1,2), thrombin-antithrombin (TAT) complexes, von Willebrand factor (vWF)] and inflammation [high-sensitivity interleukin-6 (hsIL-6), and high-sensitivity C-reactive protein (hsCRP)], measured at baseline and after 6 weeks' of rivaroxaban treatment.. There was a significant decrease in the mean levels of hsCRP, D-dimer, vWF, and TAT from baseline to end of treatment with rivaroxaban. Although none of the thrombogenesis/fibrinolysis biomarkers showed a significant relationship with thrombus resolution, high inflammatory biomarkers at baseline were significantly associated with an increased chance of the thrombus being completely resolved (hsIL-6) or reduced/resolved (hsCRP).. Biomarkers of inflammation are significantly associated with LA/LAA thrombus outcomes in AF patients prospectively treated with rivaroxaban.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Atrial Flutter; Biomarkers; Echocardiography; Female; Fibrinolysis; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Prospective Studies; Rivaroxaban; Thrombosis

The risks of intracranial haemorrhage (ICH) associated with antithrombotic drugs outside clinical trials are gaining increased attention. The aim of this nationwide study was to investigate the risk of ICH requiring hospital admission in users of antithrombotic drugs.. Data from the Norwegian Patient Registry and Norwegian Prescription Database were linked on an individual level. The primary outcome was incidence rates of ICH associated with use of antithrombotic drugs. Secondary endpoints were risk of ICH and fatal outcome following ICH assessed by Cox models. Among 3,131,270 individuals ≥18 years old observed from 2008 through 2014, there were 729,818 users of antithrombotic medications and 22,111 ICH hospitalizations. Annual crude ICH rates per 100 person-years were 0.076 (95% CI, 0.075-0.077) in non-users and 0.30 (95% CI, 0.30-0.31) in users of antithrombotic medication, with the highest age and sex adjusted rates observed for aspirin-dipyridamole plus clopidogrel (0.44; 95% CI, 0.19-0.69), rivaroxaban plus aspirin (0.36; 95% CI, 0.16-0.56), warfarin plus aspirin (0.34; 95% CI, 0.26-0.43), and warfarin plus aspirin and clopidogrel (0.33; 95% CI, 0.073-0.60). With no antithrombotic medication as reference, the highest adjusted hazard ratios (HR) for ICH were observed for aspirin-dypiridamole plus clopidogrel (6.29; 95% CI 3.71-10.7), warfarin plus aspirin and clopidogrel (4.38; 95% CI 2.71-7.09), rivaroxaban plus aspirin (3.82; 95% CI, 2.46-5.95), and warfarin plus aspirin (3.40; 95% CI, 2.99-3.86). All antithrombotic medication regimens were associated with an increased risk of ICH, except dabigatran monotherapy (HR 1.20; 95% CI, 0.88-1.65) and dabigatran plus aspirin (HR 1.79; 95% CI, 0.96-3.34). Fatal outcome within 90 days was more common in users (2,603 of 8,055) than non-users (3,228 of 14,056) of antithrombotic medication (32.3% vs 23.0%, p<0.001), and was associated with use of warfarin plus aspirin and clopidogrel (HR 2.89; 95% CI, 1.49-5.60), warfarin plus aspirin (HR 1.37; 95% CI, 1.11-1.68), aspirin plus clopidogrel (HR 1.30; 95% CI, 1.05-1.61), and warfarin (HR 1.19; 95% CI, 1.09-1.31). Increased one-year mortality was observed in users of antithrombotic medication following hemorrhagic stroke, subdural hemorrhage, subarachnoid hemorrhage, and traumatic ICH (all p<0.001). Limitations include those inherent to observational studies including the inability to make causal inferences, certain assumptions regarding drug exposure, and the possibility of residual confounding.. The real-world incidence rates and risks of ICH were generally higher than reported in randomized controlled trials. There is still major room for improvement in terms of antithrombotic medication safety (clinicaltrials.gov NCT02481011).

Topics: Adolescent; Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Male; Middle Aged; Norway; Pharmacoepidemiology; Risk Factors; Rivaroxaban; Thrombosis; Warfarin

The GEMINI-ACS-1 trial has recently been published. It was designed to test whether low dose rivaroxaban as an antithrombotic agent is as safe as aspirin in patients with acute coronary syndromes (ACS). The trial is important to set light to future of ACS management.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Humans; Rivaroxaban; Thrombosis

In global admission studies (RECORD I-IV) Rivaroxaban and enoxaparin as a standard prophylaxis were comparable in safety of treatment, but rivaroxaban appeared more effective in prevention of venous thromboembolism (VTE) when used in elective hip and knee replacement. The worldwide non-interventional cohort study XAMOS confirmed these results in the clinical routine compared to proven anticoagulants.. Efficacy and safety of rivaroxaban was to be compared with the standard prophylaxis in the prevention of VTE after elective hip and knee replacement surgery in clinical practice in Germany. For this purpose a subanalysis of the 2,719 patients (XAMOS-DE) included in XAMOS in German study centers was performed.. Out of 2,719 patients in 32 study centers 1,333 patients obtained rivaroxaban and 1,386 patients obtained standard prophylaxis. The incidence of symptomatic VTE-events (0.9% with rivaroxaban vs. 1.1% with standard prophylaxis) and severe bleeding by RECORD (0.5% vs. 0.9%) and EMA criteria (2.9 % vs. 3.0%) was similar in both groups. Most of the patients treated with rivaroxaban rated tolerability as "very good" and therapy as "very patient-friendly".. The results from XAMOS-DE confirm in clinical practice the favorable benefit-risk ratio of rivaroxaban, as well as the current S3 guidelines for thromboembolism prophylaxis with rivaroxaban in elective hip and knee replacement.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Germany; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Thrombosis

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

Livedoid vasculopathy is a thrombotic skin disease characterised by recurrent occlusion of the cutaneous microcirculation in lower extremities, which results in skin infarctions with painful ulcerations and irreversible scar formation. Rivaroxaban is a direct factor Xa inhibitor that prevents thrombus formation. We investigated whether rivaroxaban is effective for the treatment of livedoid vasculopathy.. We did this single-arm, open-label, multicenter, phase 2a, proof-of concept trial at three university hospitals in Germany. Patients with livedoid vasculopathy and a minimum pain score of 40 on the visual analogue scale were eligible to participate. Patients received oral rivaroxaban tablets for 12 weeks at an initial dose of 10 mg twice per day, which was reduced to once per day if a reduction of pain by 50% on the visual analogue scale was achieved. Subcutaneous enoxaparin at 1 mg per kg bodyweight once or twice per day was allowed as a backup treatment in case of insufficient efficacy and increased pain. The primary endpoint was change in pain on the visual analogue scale from baseline to 12 weeks. Efficacy was assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. This trial is registered with the EU Clinical Trials Register, EudraCT number 2012-000108-13-DE, and is closed to new participants.. Between Dec 28, 2012, and April 24, 2014, 36 patients were screened, 28 patients were recruited for the study, and 25 patients received treatment. During treatment, five patients dropped out of the study because of withdrawal of consent (one patient), lack of compliance (one patient), violation of inclusion criteria (two patients), and a serious adverse event (one patient). Median pain on the visual analogue scale decreased from 65·0 (IQR 52·0-78·0) at baseline to 6·0 (1·0-14·0) after 12 weeks of treatment (p<0·0001). Six of the 20 patients required additional treatment with enoxaparin. Eight treatment-related adverse events were recorded in six (24%) of the 25 patients: five cases of menorrhagia including one classified as both menorrhagia and dysmenorrhoea, one case of dyspnoea, and one case of gingival bleeding. The only serious adverse reaction to rivaroxaban during the study was one case of menorrhagia in a patient with concomitant endometriosis, which resulted in study discontinuation.. Rivaroxaban seems to effectively reduce pain in livedoid vasculopathy. Therefore we suggest that rivaroxaban with enoxaparin as a backup treatment is a suitable treatment option for patients with livedoid vasculopathy.. Deutsche Forschungsgemeinschaft and Bayer Vital.

Topics: Administration, Oral; Adult; Aged; Enoxaparin; Factor Xa Inhibitors; Female; Germany; Humans; Male; Middle Aged; Rivaroxaban; Skin Diseases; Thrombosis; Treatment Outcome

Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.. This randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily. Randomisation was done centrally, stratified by centre and patient type (with vs without systemic lupus erythematosus). The primary outcome was percentage change in endogenous thrombin potential (ETP) from randomisation to day 42, with non-inferiority set at less than 20% difference from warfarin in mean percentage change. Analysis was by modified intention to treat. Other thrombin generation parameters, thrombosis, and bleeding were also assessed. Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation. This trial is registered with the ISRCTN registry, number ISRCTN68222801.. Of 116 patients randomised between June 5, 2013, and Nov 11, 2014, 54 who received rivaroxaban and 56 who received warfarin were assessed. At day 42, ETP was higher in the rivaroxaban than in the warfarin group (geometric mean 1086 nmol/L per min, 95% CI 957-1233 vs 548, 484-621, treatment effect 2·0, 95% CI 1·7-2·4, p<0·0001). Peak thrombin generation was lower in the rivaroxaban group (56 nmol/L, 95% CI 47-66 vs 86 nmol/L, 72-102, treatment effect 0·6, 95% CI 0·5-0·8, p=0·0006). No thrombosis or major bleeding were seen. Serious adverse events occurred in four patients in each group.. ETP for rivaroxaban did not reach the non-inferiority threshold, but as there was no increase in thrombotic risk compared with standard-intensity warfarin, this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism.. Arthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prevalence; Rivaroxaban; Survival Rate; Thrombosis; Treatment Outcome; United Kingdom; Warfarin

Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers.. In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication.. The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up.. On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .).

Topics: Acute Disease; Aged; Aged, 80 and over; Cardiovascular Diseases; Enoxaparin; Factor Xa; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Infusions, Intravenous; Intracranial Hemorrhages; Male; Prospective Studies; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Thrombosis

Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown.. Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA.. With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.

Topics: Aged; Atrial Fibrillation; Atrial Flutter; Atrial Function, Left; Dabigatran; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Vitamin K

There are still many unresolved issues concerning patient outcomes and prognostic factors in patients with atrial fibrillation (AF) and left atrial/left atrial appendage (LA/LAA) thrombi. Rivaroxaban (Xarelto®), a potent and highly selective oral, direct factor Xa inhibitor, is a new therapeutic option in this setting. The planned study program will consist of a prospective interventional study (X-TRA) and a retrospective observational registry (CLOT-AF). The primary objective of the X-TRA study is to explore the efficacy of rivaroxaban in the treatment of LA/LAA thrombi in patients with nonvalvular AF or atrial flutter, scheduled to undergo cardioversion or AF ablation, in whom an LA/LAA thrombus has been found on transesophageal echocardiography (TEE) before the procedure. The primary end point is the complete LA/LAA thrombus resolution rate at 6 weeks of end of treatment confirmed by TEE. The secondary objectives are to describe categories of thrombus outcome in patients (resolved, reduced, unchanged, larger, or new) confirmed on TEE at the end of treatment (after 6 weeks of treatment), incidence of the composite of stroke and noncentral nervous system systemic embolism at the end of treatment and during follow-up, and incidence of all bleeding at the end of treatment and during follow-up. The objective of the CLOT-AF registry is to provide retrospective thrombus-related patient outcome data after standard-of-care anticoagulant treatment in patients with nonvalvular AF or atrial flutter, who have TEE-documented LA/LAA thrombi. The data will be used as a reference for the prospective X-TRA study. In conclusion, X-TRA and CLOT-AF will provide some answers to the many unresolved issues concerning patient outcomes and prognostic factors in patients with AF and LAA thrombi. Results from this study program would provide the first prospective interventional study (X-TRA) and a large international retrospective observational registry (CLOT-AF) on the prevalence and natural history of LA/LAA thrombi. Unique data on clot resolution with rivaroxaban in a prospective cohort would be obtained in X-TRA.

Topics: Administration, Oral; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography, Transesophageal; Electric Countershock; Factor Xa Inhibitors; Female; Heart Diseases; Humans; Male; Middle Aged; Morpholines; Retrospective Studies; Rivaroxaban; Thiophenes; Thrombosis; Treatment Outcome

Patients on rivaroxaban requiring percutaneous coronary intervention (PCI) represent a clinical conundrum. We aimed to investigate whether rivaroxaban, with or without an additional bolus of unfractionated heparin (UFH), effectively inhibits coagulation activation during PCI. Stable patients (n=108) undergoing elective PCI and on stable dual antiplatelet therapy were randomised (2:2:2:1) to a short treatment course of rivaroxaban 10 mg (n=30), rivaroxaban 20 mg (n=32), rivaroxaban 10 mg plus UFH (n=30) or standard peri-procedural UFH (n=16). Blood samples for markers of thrombin generation and coagulation activation were drawn prior to and at 0, 0.5, 2, 6-8 and 48 hours (h) after start of PCI. In patients treated with rivaroxaban (10 or 20 mg) and patients treated with rivaroxaban plus heparin, the levels of prothrombin fragment 1 + 2 at 2 h post-PCI were 0.16 [0.1] nmol/l (median) [interquartile range, IQR] and 0.17 [0.2] nmol/l, respectively. Thrombin-antithrombin complex values at 2 h post-PCI were 3.90 [6.8]µg/l and 3.90 [10.1] µg/l, respectively, remaining below the upper reference limit (URL) after PCI and stenting. This was comparable to the control group of UFH treatment alone. However, median values for thrombin-antithrombin complex passed above the URL with increasing tendency, starting at 2 h post-PCI in the UFH-alone arm but not in rivaroxaban-treated patients. In this exploratory trial, rivaroxaban effectively suppressed coagulation activation after elective PCI and stenting.

Topics: Aged; Anticoagulants; Antithrombin III; Biomarkers; Coronary Disease; Drug Therapy, Combination; Elective Surgical Procedures; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Complications; Prothrombin; Risk Factors; Rivaroxaban; Single-Blind Method; Stents; Thrombin; Thrombosis

No routine monitoring is required with factor Xa inhibitor rivaroxaban. Yet, its titration must be adapted, and its misuse may lead to increased risk of bleeding; therefore, therapeutic rivaroxaban monitoring might help in specific situations.. As asked by clinicians of our medical center, we measured rivaroxaban plasma concentrations in real conditions of use and checked their corresponding prescriptions. Measurement of 112 samples from 94 consecutive patients was performed with a Biophen LRT® anti-Xa chromogenic assay and compared blindly to the HPLC-MSMS "gold standard" method. Rivaroxaban was effectively given to 80 out of 94 patients but a mere 57% through an adequate prescription (within the scope of indications/titration). All chromogenic measurements were over the pre-specified 30ng/ml LOQ, whereas only 98 /114 samples had quantifiable rivaroxaban with HPLC-MSMS (LOQ 1ng/ml). Correlation between the two methods and linear regression were highly significant (p<0.0001). However, chromogenic values (mean 141.6ng/ml[96.6]) overestimated HPLC-MSMS values (119.7ng/ml[79.5]) by 22ng/ml according to Bland-Altman analysis (p<0.001). After re-assessing the chromogenic LOQ at 52ng/ml, 83 quantifiable samples had a mean concentration of 176.9ng/ml as compared to 158.5ng/ml with HPLC-MSMS, with no false positive anymore.. In our medical center, rivaroxaban concentrations could be assessed by a rapid chromogenic method. Its pre-specified LOQ proved too high after being checked "on site" against HPLC-MSMS. Prescriptions for rivaroxaban were not optimal. An overestimated LOQ may impair observance monitoring or predispose patients to either risky thrombolysis or otherwise adjournable surgery in clinical practice.

Topics: Aged; Blood Chemical Analysis; Chromogenic Compounds; Colorimetry; Factor Xa; Factor Xa Inhibitors; Female; Humans; Male; Reproducibility of Results; Rivaroxaban; Sensitivity and Specificity; Single-Blind Method; Thrombosis

Patients with acute coronary syndrome and concomitant atrial fibrillation may require antithrombotic triple therapy but clinical evidence of safety and efficacy is poor. We have therefore studied the combination of different antithrombotic medicines for coagulation activation in an in vivo model in the skin microvasculature.. Platelet activation (β-thromboglobulin [β-TG]) and thrombin generation (prothrombin fragment 1 + 2 [F1+2 ], thrombin-antithrombin complex [TAT]) were studied in an open-label, randomized, parallel group trial in 60 healthy male subjects (n = 20 per group) who received ticagrelor and acetylsalicylic acid (ASA) in combination with dabigatran (150 mg bid), rivaroxaban (20 mg od) or phenprocoumon (INR 2.0-3.0). Coagulation biomarkers in shed blood were assessed at 3 h after monotherapy with the medicines under study, at 3 h after triple therapy dosing and at steady state trough conditions. Single doses of ticagrelor, dabigatran or rivaroxaban caused comparable decreases in shed blood β-TG and were more pronounced than phenprocoumon at an INR of 2.0-3.0. In contrast, thrombin generation was more affected by rivaroxaban and phenprocoumon than by dabigatran. During triple therapy a similarly sustained inhibition of platelet activation and thrombin generation with a maximum decrease of β-TG, F1+2 and TAT at 3 h post-dosing was noted, which remained below pre-dose levels at trough steady state.. A triple therapy at steady state with ticagrelor plus ASA in combination with dabigatran or rivaroxaban is as effective as a combination with phenprocoumon for platelet activation and thrombin generation in vivo.

Topics: Adenosine; Administration, Oral; Adult; Anticoagulants; Antithrombin III; Aspirin; Austria; Benzimidazoles; beta-Alanine; beta-Thromboglobulin; Biomarkers; Blood Coagulation; Blood Platelets; Dabigatran; Drug Therapy, Combination; Fibrinolytic Agents; Healthy Volunteers; Humans; International Normalized Ratio; Male; Morpholines; Peptide Fragments; Peptide Hydrolases; Phenprocoumon; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Prothrombin; Rivaroxaban; Thiophenes; Thrombin; Thrombosis; Ticagrelor; Young Adult

The aim of this study was to determine if rivaroxaban is associated with a reduction in stent thrombosis among patients with acute coronary syndromes (ACS) in the ATLAS-ACS 2 TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51) trial.. Dual antiplatelet therapy (DAPT) has been the mainstay of efforts to prevent stent thrombosis. Because thrombin is a potent stimulant of platelet activation, we hypothesized that inhibition of thrombin generation via factor Xa inhibition may further reduce the risk of stent thrombosis.. The ATLAS-ACS 2 TIMI 51 study was a placebo-controlled trial that randomly assigned 15,526 patients with recent ACS to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months.. Among patients who had a stent placed before or at the time of the index event, rivaroxaban significantly reduced independently adjudicated Academic Research Consortium definite and probable stent thrombosis in the pooled (1.9% vs. 1.5%; hazard ratio [HR]: 0.65; p = 0.017) and the 2.5 mg twice-daily (1.9% vs. 1.5%; HR: 0.61; p = 0.023) treatment groups when compared with placebo, with a trend toward a reduction in the 5 mg twice-daily treatment group (1.9% vs. 1.5%; HR: 0.70; p = 0.089). Among patients who received both aspirin and a thienopyridine (stratum 2), the benefit of rivaroxaban emerged during the period of active treatment with DAPT (HR: 0.68; 95% CI: 0.50 to 0.92, combined rivaroxaban group vs. placebo). Among stented patients who were treated with dual antiplatelet therapy, there was a mortality reduction among those treated with twice-daily rivaroxaban 2.5 mg (HR: 0.56; 95% CI: 0.35 to 0.89; p = 0.014).. Among stented patients with ACS treated with DAPT, the administration of twice-daily rivaroxaban 2.5 mg was associated with a reduction in stent thrombosis and mortality. (An Efficacy and Safety Study for Rivaroxaban in Patients With Acute Coronary Syndrome; NCT00809965).

Topics: Acute Coronary Syndrome; Aged; Aspirin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Platelet Aggregation Inhibitors; Pyridines; Rivaroxaban; Stents; Thiophenes; Thrombosis; Treatment Outcome

Rivaroxaban, a direct factor Xa inhibitor, has demonstrated effectiveness for the management of both venous and arterial thrombosis. This study was designed to investigate the antithrombotic effect of rivaroxaban, with or without acetylsalicylic acid (ASA), in an ex vivo perfusion chamber at both low and high shear rates.. Healthy subjects (N=51) were enrolled in a randomized, crossover (rivaroxaban 5, 10 or 20mg with or without ASA), and parallel-group (compared with ASA plus clopidogrel) study. Thrombi formed on pig aorta strips were measured after a 5-minute perfusion at low and high shear rates with blood from the subjects by measuring D-dimer concentration (for fibrin deposition) and P-selectin content (for platelet deposition).. ASA alone had no impact on thrombus D-dimer levels, whereas rivaroxaban alone at peak concentrations decreased D-dimer levels by 9%, 84% and 65% at low shear rate and 37%, 73% and 74% at high shear rate after doses of 5, 10 and 20mg, respectively. Steady-state ASA plus rivaroxaban 5mg caused a greater reduction in D-dimer levels (63%) than monotherapy at low shear rate. Co-administration of ASA with clopidogrel was associated with a 30% decrease in D-dimer levels at low shear rate and a 14% decrease at high shear rate. No conclusive effect on P-selectin content was observed across the treatment groups.. Rivaroxaban dose-dependently inhibited ex vivo thrombus formation under low and high shear rates. Co-administration of ASA had an additional effect on the antithrombotic action of low-dose rivaroxaban.

Topics: Adolescent; Adult; Animals; Anticoagulants; Aspirin; Cross-Over Studies; Female; Humans; In Vitro Techniques; Male; Middle Aged; Morpholines; Platelet Aggregation; Rivaroxaban; Swine; Thiophenes; Thrombosis; Venous Thromboembolism; Young Adult

Perioperative blood loss is a frequent cause of complications in total hip replacement (THR). The present prospective study assessed the efficacy of tranexamic acid (Exacyl(®)) in reducing blood loss in primary THR associated to rivaroxaban (Xarelto(®)) thromboprophylaxis.. Tranexamic acid associated to rivaroxaban reduces blood loss.. A prospective case-control study included 70 primary cementless THRs performed by a single surgeon on a standardized technique, between September 2009 and September 2010. Thirty-seven patients received perioperative tranexamic acid; all patients received rivaroxaban thromboprophylaxis.. There was no significant difference between the two groups in terms of peroperative blood-loss volume or rates of thromboembolic or ischemic events or hematoma. Postoperative blood loss, D0-5 differential hemoglobinemia and real blood loss (in mL 100% hematocrit) were significantly lower in the tranexamic acid group. No transfusions were required in the tranexamic acid group, versus four in the control group.. Tranexamic acid associated to direct anti-Xa (antithrombin-independent) oral anticoagulants was effective in reducing postoperative blood loss, improving hemoglobinemia at 5 days and reducing transfusion rates. The results also confirmed the efficacy of and tolerance for rivaroxaban thromboprophylaxis in primary THR, with no clinical thrombotic events induced by the association of tranexamic acid with rivaroxaban.. Tranexamic acid is a simple means of reducing postoperative blood loss in THR, without increased risk of thromboembolism when associated to rivaroxaban thromboprophylaxis.. Level III prospective case-control study.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Arthroplasty, Replacement, Hip; Bone Cements; Case-Control Studies; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Morpholines; Postoperative Hemorrhage; Prospective Studies; Prostheses and Implants; Rivaroxaban; Single-Blind Method; Thiophenes; Thrombosis; Tranexamic Acid; Treatment Outcome

Plasma proteins mediate thrombogenesis, inflammation, endocardial injury and structural remodelling in atrial fibrillation (AF). We hypothesised that anti-coagulation with rivaroxaban, a direct factor Xa inhibitor, would differentially modulate biologically-relevant plasma proteins, compared with warfarin, a multi-coagulation protein antagonist. We performed unbiased liquid chromatography/tandem mass spectroscopy and candidate multiplexed protein immunoassays among Japanese subjects with non-valvular chronic AF who were randomly assigned to treatment with 24 weeks of rivaroxaban (n=93) or warfarin (n=94). Nine metaproteins, including fibulin-1 (p=0.0033), vitronectin (p=0.0010), haemoglobin α (p=0.0012), apolipoproteins C-II (p=0.0017) and H (p=0.0023), complement C5 precursor (p=0.0026), coagulation factor XIIIA (p=0.0026) and XIIIB (p=0.0032) subunits, and 10 candidate proteins, including thrombomodulin (p=0.0004), intercellular adhesion molecule-3 (p=0.0064), interleukin-8 (p=0.0007) and matrix metalloproteinase-3 (p=0.0003), were differentially expressed among patients with and without known clinical risk factors for stroke and bleeding in AF. Compared with warfarin, rivaroxaban treatment was associated with a greater increase in thrombomodulin (Δ 0.1 vs. 0.3 pg/ml, p=0.0026) and a trend towards a reduction in matrix metalloproteinase-9 (Δ 2.2 vs. -4.9 pg/ml, p=0.0757) over 24 weeks. Only modest correlations were observed between protein levels and prothrombin time, factor Xa activity and prothrombinase-induced clotting time. Plasma proteomics can identify distinct functional patterns of protein expression that report on known stroke and bleeding risk phenotypes in an ethnically-homogeneous AF population. The greater upregulation of thrombomodulin among patients randomised to rivaroxaban represents a proof-of-principle that pharmacoproteomics can be employed to discern novel effects of factor Xa inhibition beyond standard pharmacodynamic measures.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Blood Proteins; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Morpholines; Proteomics; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Warfarin

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

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

Patients with a mechanical heart valve need a lifelong anticoagulation due to the increased risk of valve thrombosis and thrombo-embolism. Currently, vitamin K antagonists (VKA) are the only approved class of oral anticoagulants, but relevant interactions and side effects lead to a large number of patients not achieving the optimal therapeutic target international normalized ration (INR). Therefore, steady measurements of the INR are imperative to ensure potent anticoagulation within a distinctive range. Direct oral anticoagulants (DOACs) with newer agents could serve as a possible alternative to VKAs in this patient cohort. DOACs are approved for several indications, e.g., atrial fibrillation (AF). They only have a minor interaction potential, which is why monitoring is not needed. Thereby, DOACs improve the livability of patients in need of chronical anticoagulation compared with VKAs. In contrast to dual platelet inhibition using aspirin in combination with an ADP receptor antagonist and the direct thrombin inhibitor dabigatran, the oral factor Xa inhibitors apixaban and rivaroxaban show promising results according to current evidence. In small-scale studies, factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients with mechanical heart valves. Finally, DOACs seem to represent a feasible treatment option in patients with mechanical heart valves, but further studies are needed to evaluate clinical safety. In addition to the ongoing PROACT Xa trial with apixaban in patients after aortic On-X valve implantation, studies in an all-comer collective with rivaroxaban could be promising.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Heart Valves; Humans; Rivaroxaban; Stroke; Thrombosis; Treatment Outcome

The purpose of this study was to evaluate and compare clinical outcomes in patients who experienced intracranial hemorrhage (ICH) while taking apixaban or rivaroxaban and were reversed with four-factor prothrombin complex concentrates (4F-PCC) or andexanet alfa (AA). This retrospective cohort included adult patients that received 4F-PCC or AA for the initial management of an apixaban- or rivaroxaban-associated ICH. A primary outcome of excellent or good hemostatic efficacy at 12 h post-reversal was assessed. Secondary outcomes evaluated were change in hematoma volume size at 12 h, functional status at discharge, need for surgical intervention or additional hemostatic agents post-reversal, new thrombotic event within 28 days, 28-day all-cause mortality, discharge disposition, and hospital and intensive care unit lengths of stay. A total of 70 patients were included (4F-PCC, n = 47; AA, n = 23). For the primary outcome analysis, 21 patients were included in the 4F-PCC group and 12 in the AA group. The rate of effective hemostasis was similar between the 4F-PCC and AA groups (66.7% vs 75%, p = 0.62). There were no statistically significant differences between the groups for secondary outcomes, including 28-day mortality (40.4% vs 39.1%, p = 0.92) and thrombotic complications within 28 days of reversal (17.0% vs 21.7%, p = 0.63). In patients who experienced an ICH while taking apixaban or rivaroxaban, 4F-PCC and AA were found to have similar rates of excellent or good hemostatic efficacy.

Topics: Adult; Anticoagulants; Blood Coagulation Factors; Factor IX; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Intracranial Hemorrhages; Recombinant Proteins; Retrospective Studies; Rivaroxaban; Thrombosis

Central venous catheters are prone to clotting, particularly in patients with cancer. Although low-molecular-weight heparin and direct oral anticoagulants, such as apixaban and rivaroxaban, have been evaluated for the prevention of catheter thrombosis, their efficacy remains uncertain.. Compare apixaban and rivaroxaban with enoxaparin for the prevention of catheter-induced clotting in vitro.. To address this uncertainty, we used a well-established microplate-based assay to compare the effects of enoxaparin, apixaban, and rivaroxaban on catheter-induced thrombosis and thrombin generation in human plasma.. Consistent with our previous findings, catheter segments shortened the clotting time and promoted thrombin generation. When compared at concentrations with similar anti-factor Xa activity as enoxaparin, apixaban and rivaroxaban were >20-fold less potent than enoxaparin for the prevention of catheter-induced clotting and thrombin generation.. The prevention of catheter thrombosis in patients with cancer is challenging. Clinical trials are needed to compare the efficacy of low-molecular-weight heparin with that of direct oral anticoagulants both for the prevention and treatment of catheter thrombosis.

Topics: Anticoagulants; Catheters; Enoxaparin; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridones; Rivaroxaban; Thrombin; Thrombosis

Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting.. To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients.. The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests.. Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups.. The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.. Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial.. Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19.. O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos.. Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento.. O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Topics: Adult; Anticoagulants; Brazil; COVID-19; Endothelial Cells; Fibrinolytic Agents; Humans; Outpatients; Randomized Controlled Trials as Topic; Rivaroxaban; SARS-CoV-2; Thrombosis; Treatment Outcome; Venous Thromboembolism

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Humans; Rivaroxaban; Stroke; Thrombosis; Treatment Outcome; Warfarin

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

Three dogs were diagnosed with right atrial thrombosis, thought to be secondary to systemic diseases. Specifically, two cases had hyperadrenocorticism and one case was diagnosed with pancreatitis with acute renal injury. In all cases, the thrombi were found within the right atrium, necessitating a differentiation from cardiac neoplasia. In all three cases, the structures assumed to be thrombi had irregular margins with interspersed hypoechoic regions, which were later confirmed as thrombi based on the responsiveness to therapy. All three cases were prescribed with the combination of clopidogrel and rivaroxaban.The thrombi gradually disappeared after initiation of the combination therapy. Complete resolution of right atrial thrombosis was noted in each dog treated with clopidogrel and rivaroxaban. This combination therapy appears to be safe and well tolerated. Diligent observation of the echocardiographic findings and clinical course allows the diagnosis of thrombosis.

Topics: Animals; Atrial Fibrillation; Clopidogrel; Dog Diseases; Dogs; Echocardiography; Fibrinolytic Agents; Follow-Up Studies; Heart Atria; Heart Diseases; Rivaroxaban; Thrombosis

Andexanet alfa is a Gla-domainless FXa (GDXa) analog used as an antidote to FXa inhibitors. Despite its clinical use, laboratory monitoring for anti-Xa reversal and the effect of andexanet on fibrinolysis has not been explored. We used a GDXa with a serine-to-alanine mutation at position 195 (chymotrypsin numbering) to model the interaction between andexanet and apixaban.. Six batches of pooled plasma, and whole blood from healthy volunteers were treated with increasing concentrations of apixaban with/without GDXa. Thrombin generation and plasmin generation (TG and PG) were tested in plasma, and whole blood thrombus formation was tested using thromboelastometry or a flow-chamber system. FXa was also tested in isolation for its ability to support plasmin activation with/without apixaban and GDXa.. Apixaban (250-800 nM) concentration-dependently decreased the velocity and peak of TG in plasma. Apixaban prolonged the onset of thrombus formation in thromboelastometry and flow-chamber tests. GDXa normalized apixaban-induced delays in TG and whole blood thrombus formation. However, GDXa minimally affected the low PG velocity and peak caused by apixaban at higher concentrations (500-800 nM). FXa promoted plasmin generation independent of fibrin that was inhibited by apixaban at supratherapeutic concentrations.. This study demonstrated the feasibility of assessing coagulation lag time recovery in plasma and whole blood following in vitro apixaban reversal using GDXa, a biosimilar to andexanet. In contrast, GDXa-induced changes in plasmin generation and fibrinolysis were limited in PG and tPA-added ROTEM assays, supporting the endogenous profibrinolytic activity of FXa and its inhibition at elevated apixaban concentrations.

Topics: Blood Coagulation; Factor Xa; Factor Xa Inhibitors; Fibrinolysin; Humans; Pyridones; Rivaroxaban; Thrombosis

Clinical trials comparing direct oral anticoagulants (DOAC) to warfarin excluded patients with a history of bariatric surgery. The anatomic changes from bariatric procedures have several effects on drug absorption which can have serious consequences for these patients. We sought to describe real-world use of DOACs among adults that had a history of bariatric surgery or underwent a bariatric surgery while receiving a DOAC. We conducted a retrospective case series of adult patients, at a large academic medical center, who initiated any DOAC in 2016 thru 2019 and had a history of bariatric surgery or underwent a bariatric surgery while receiving a DOAC. Thrombotic and bleeding events were described using summary statistics and bleeding severity was described using the International Society on Thrombosis and Haemostasis criteria. Twenty-eight patients met the inclusion criteria of having bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy or gastric band) and receiving a DOAC. Twenty (71.4%) were prescribed apixaban and eight (28.6%) were prescribed rivaroxaban. Seven patients (25%) experienced at least one clinically relevant non-major bleeding event, including one patient (3.6%) that had a major bleeding event. Two patients (7.1%) had a thromboembolic event. Coagulation laboratory studies were infrequently performed at the time of the bleeding or clotting events. Among patients with a history of bariatric surgery, use of DOACs were commonly associated with clinically relevant non-major bleeding events and less commonly associated with major bleeding and thromboembolic events. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in patients that have undergone bariatric surgery. The specific role of coagulation laboratory studies warrants further evaluation.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Bariatric Surgery; Dabigatran; Hemorrhage; Humans; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thromboembolism; Thrombosis

Anticoagulant therapy is suggested within 45 days after Watchman device implantation for stroke prevention in patients with atrial fibrillation (AF). A previous study demonstrated that non-vitamin K antagonist oral anticoagulants (NOACs) were a feasible peri- and postprocedural alternative to warfarin. The present study aimed to compare the safety and efficacy of using different anticoagulants (low-dose NOACs vs. warfarin) within 45 days after Watchman device implantation in a Chinese population.. Patients with successful Watchman device implantation from October 2014 to June 2020 were included. All patients received anticoagulants within 45 days after the procedure, and those patients were divided into three groups according to the type of postprocedural anticoagulants. Transesophageal echocardiography follow-up was performed 45 days post procedure to assess residual flow and the occurrence of device-related thrombus (DRT).. A total of 368 patients were enrolled in the study. The study population was divided into three groups: the warfarin group (n = 77), the dabigatran group (n = 165) and the rivaroxaban group (n = 126). Periprocedural major bleeding was higher in the warfarin group (2.6% vs. 0% vs. 0%, P = 0.043), while minor bleeding was comparable among the groups (3.9% vs. 1.2% vs. 0.8%, P = 0.230). No periprocedural transient ischemic attack/stroke occurred. At follow-up, the incidence of DRT was higher in the warfarin group than in the other groups (4.2% vs. 0.6% vs. 0.8%; P = 0.116), but the difference was not statistically significant. The rates of thromboembolic and bleeding events were similar in the three groups.. The safety and efficacy of low-dose dabigatran and rivaroxaban were comparable to those of warfarin within 45 days after Watchman device implantation in a Chinese population.

Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Rivaroxaban; Stroke; Thrombosis; Treatment Outcome; Warfarin

Warfarin is recognized as the standard treatment for thrombotic antiphospholipid syndrome (APS); however, direct oral anticoagulants (DOACs) represent appealing therapeutic alternatives given their lack of monitoring and limited drug interactions. A few randomized controlled trials comparing rivaroxaban with warfarin showed an increased risk of recurrent thromboembolism, specifically arterial thrombosis, in patients with high risk forms of APS such as those that are triple antibody positive. We conducted a single-center, retrospective cohort study of all patients within our health system from 2015 to 2020 with a diagnosis of APS (single or double antibody positive) and history of venous thromboembolism. We sought to compare the proportion of patients with a recurrent thrombosis when prescribed a DOAC versus warfarin. Among 96 patients included, 57 were prescribed warfarin and 39 were prescribed a DOAC (90% rivaroxaban). The proportion of patients with a recurrent thromboembolism was almost three times higher in the DOAC group (15.4%) compared to the warfarin group (5.3%), although this was not statistically significant (p = 0.15). Major bleeding was not different between groups. Our findings suggest that rivaroxaban may pose an increased risk for recurrent thromboembolism in low risk APS patients that are single or double-antibody positive compared to warfarin. Results of our study should be cautiously applied to DOACs besides rivaroxaban given their small representation in this study.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Retrospective Studies; Rivaroxaban; Thrombosis; Venous Thromboembolism; Warfarin

Direct oral anticoagulants (DOACs) represent an off-label but potential alternative to traditional therapies for heparin-induced thrombocytopenia (HIT).. The objective of this study was to evaluate the efficacy and safety of DOACs in patients with a diagnosis of laboratory-confirmed HIT.. A multicenter retrospective cohort study of adult patients with HIT treated with apixaban, rivaroxaban, or dabigatran between 1 January 2013 and 1 January 2020 was performed. Patients with an intermediate or high pre-test probability for HIT and a positive antiplatelet factor 4/heparin complex assay, latex immunoturbidimetric assay, or serotonin release assay were included for analysis. The primary outcome was the composite of newly diagnosed venous or arterial thromboembolism, gangrene, or severe limb ischemia requiring amputation at 3 months following DOAC initiation. This study was approved by local institutional review boards, and the requirement for informed consent was waived.. A total of 77 patients from four health systems were included. The median 4Ts score was 5 (interquartile range 4.5-6), and 38 patients (49.4%) had a diagnosis of HIT with thrombosis. The most frequently used DOAC was apixaban (n = 51), followed by rivaroxaban (n = 24) and dabigatran (n = 2). In total, 63 (81.8%) patients received parenteral non-heparin anticoagulation prior to DOAC initiation. Nine patients (11.7%) experienced the primary outcome of HIT-related thrombotic events. Of the 14 patients who exclusively received DOAC therapy, none experienced the primary outcome. Major bleeding occurred in five (6.5%) patients.. In this retrospective cohort study, DOACs were associated with rates of thrombotic and hemorrhagic events similar to those with other therapies currently used in the treatment of HIT.

Topics: Administration, Oral; Adult; Anticoagulants; Dabigatran; Hemorrhage; Humans; Retrospective Studies; Rivaroxaban; Thrombocytopenia; 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

A 45 year old male with hypertension was presented to our centre with a recent inferior wall myocardial infarction (IWMI) and post infarction angina. Invasive coronary angiography revealed an occluded proximal right coronary artery (RCA) with high thrombus burden, in the absence of obstructive disease in the remaining coronary vasculature. Based on raised platelet counts of 923,000/microliter and positive Janus kinase (JAK 2- V617) mutations tested by polymerase chain reaction (PCR), a diagnosis of essential thrombocythemia (ET) was made. A therapeutic strategy of aspiration thrombectomy along with I/V Tirofiban was used for three days, followed by reassessed angiogram and percutaneous coronary intervention (PCI) with drug eluting stent (DES) placement was applied. In addition to dual antiplatelet and statin therapy, patient was treated with Rivaroxaban 15 mg once daily for a month and Hydroxyurea 500mg twice daily. At one month follow up, patient was asymptomatic, with decreasing platelet counts and no bleeding complications.

Topics: Coronary Vessels; Drug-Eluting Stents; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Rivaroxaban; Thrombocythemia, Essential; Thrombosis; Tirofiban

Topics: Anticoagulants; Humans; Rivaroxaban; Thrombosis; Treatment Outcome

Heparin is the standard anticoagulant for cardiopulmonary bypass (CPB); however, there are problems with its use that make the development of suitable alternatives desirable. Currently, no ideal alternative exists. We have previously reported that the direct thrombin inhibitor dabigatran can prevent coagulation in simulated CPB at high concentrations. These high concentrations may cause difficulties in achieving the reversal of dabigatran with idarucizumab, given the markedly different pharmacokinetics of the 2 drugs. Herein, we test the hypothesis that the addition of the anti-Xa drug rivaroxaban would provide suitable anticoagulation at a lower concentration of dabigatran given likely synergy between the 2 classes of drugs. The primary goal of the study was to investigate whether the addition of rivaroxaban reduces the concentration of dabigatran necessary to allow 2 hours of simulated CPB.. The study was performed in sequential steps. Blood collected from consenting healthy donors was used throughout. First, we added graded concentrations of dabigatran and rivaroxaban alone and in combination and assessed inhibition of anticoagulation using thromboelastometry. Using results from this step, combinations of dabigatran and rivaroxaban were tested in both Chandler loop and simulated CPB circuits. Dabigatran and rivaroxaban were added before recalcification, and the circuits were run for 120 minutes. In both models of CPB, 120 minutes of circulation without visible thrombus was considered successful. In the Chandler loop system, idarucizumab was added to reverse anticoagulant effects. In the CPB circuits, the arterial line filters were examined using scanning electron microscope (SEM) to qualitatively assess for fibrin deposition.. In vitro analysis of blood samples treated with dabigatran and rivaroxaban showed that dabigatran and rivaroxaban individually prolonged clotting time (CT) in a dose-dependent manner. However, when combined, the drugs behaved synergistically. In the Chandler loop system, dabigatran 2400 and 4800 ng/mL plus rivaroxaban (150 ng/mL) effectively prevented clot formation and reduced the dynamics of clot propagation for 120 minutes. Idarucizumab (250-1000 µg/mL) effectively reversed anticoagulation. In the CPB circuits, dabigatran (2500 ng/mL) and rivaroxaban (200 ng/mL) were successful in allowing 120 minutes of simulated CPB and prevented fibrin deposition. Biomarkers of coagulation activation did not increase during simulated CPB. Heparin controls performed similarly to dabigatran and rivaroxaban.. The dual administration of oral anticoagulant drugs (dabigatran and Rivaroxaban) with different pharmacologic mechanisms of action produced synergistic inhibition of coagulation in vitro and successfully prevented clotting during simulated CPB.

Topics: Anticoagulants; Cardiopulmonary Bypass; Dabigatran; Fibrin; Heparin; Humans; Rivaroxaban; Thrombosis

To describe a population of sick dogs administered rivaroxaban monitored with a rivaroxaban-calibrated anti-Xa activity assay (aXa).. Descriptive retrospective study.. Two veterinary teaching hospitals.. Client-owned dogs administered rivaroxaban and monitored with aXa from January 2018 to January 2020 were eligible for study.. None.. Medical records were reviewed and 19 dogs with a variety of underlying disease processes were identified. Rivaroxaban was administered to 12 of 19 dogs (63%) with confirmed thrombosis, 4 of 19 dogs (21%) with a strong clinical suspicion of thrombosis, and in 3 of 19 dogs (16%) with no current evidence of thrombosis. The median rivaroxaban dose administered was 0.96 mg/kg/day (0.62-1.58 mg/kg/day), with 15 of 19 dogs (79%) receiving rivaroxaban once daily. Clopidogrel was concurrently administered to 11 of 19 dogs (58%). Complete or partial thrombus resolution was identified in 5 of 12 (42%) and 3 of 12 (25%) dogs, respectively. Rivaroxaban appeared safe, with only 1 of 19 dogs (5%), concurrently administered clopidogrel, developing evidence of mild hematuria. Posttreatment monitoring revealed that 8 of 19 dogs (42%) had aXa below the target (aXa range of 150-250 ng/ml associated with effective treatment and prevention of venous thrombosis in people). The remaining 3 to 19 dogs (16%) achieved this range, and 8 of 19 dogs (42%) exceeded the range. No significant relationship between the initial rivaroxaban dose administered and the corresponding aXa result was identified. There were also no significant differences in baseline clinicopathological variables in dogs in which aXa fell within or outside this range.. aXa was most commonly measured in dogs receiving rivaroxaban with confirmed or suspected thrombosis. Dogs in this study received a range of rivaroxaban dosages and attained variable aXa values that were not directly correlated with dosage.

Topics: Animals; Anticoagulants; Clopidogrel; Dog Diseases; Dogs; Factor Xa Inhibitors; Humans; Retrospective Studies; Rivaroxaban; Thrombosis

Topics: COVID-19; Humans; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Mesenteric Veins; Peripheral Arterial Disease; Rivaroxaban; Thrombosis

Direct oral anticoagulants (DOACs) have recently proven their efficacy and safety, as primary and secondary prevention agents for thrombosis in cancer patients. We aimed to determine if DOACs might be a suitable choice to reduce the thrombotic risk in myeloproliferative neoplasm (MPN) patients.. We analysed a large multicentric cohort of MPN patients treated with rivaroxaban or apixaban after atrial fibrillation (AF) or thrombotic events.. We included 135 MPN patients with a median follow-up of 23.8 months since DOAC initiation. Twenty patients (14.8 %) developed 30 thrombotic events (28 arterial thromboses in 19 patients) for a global incidence of 6.5 % patient-years. No difference was highlighted between apixaban and rivaroxaban in terms of thrombosis risk, but the incidence of arterial thrombosis was significantly higher on low-dose DOACs (11.9 vs. 4.5 % patient-years, p = 0.04). Bleeding events were more frequent in the full-dose group (41.2 vs. 15.2 %, p = 0.006). However, major and clinically relevant non major (CRNM) bleeding events occurred in 18 patients (13.3 %), with no difference between the groups. Age was the only identified thrombotic risk factor, whereas risk factors for major or CRNM bleeding were a full-dose treatment regimen and a combination of DOAC/low-dose aspirin.. DOACs seem effective in preventing venous thrombosis in MPN patients with AF or VTE. For these high-risk patients, low-dose DOACs exposed patients to more arterial thrombosis but fewer bleeding events. Prospective studies are needed to evaluate and compare DOACs to the currently recommended antithrombotic drugs for high-risk MPN patients.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Myeloproliferative Disorders; Neoplasms; Rivaroxaban; Thrombosis

Andexanet alfa is approved (FDA "accelerated approval"; EMA "conditional approval") as the first specific reversal agent for factor Xa (FXa) inhibitor-associated uncontrolled or life-threatening bleeding. Four-factor prothrombin complex concentrates (4F-PCC) are commonly used as an off-label, non-specific, factor replacement approach to manage FXa inhibitor-associated life-threatening bleeding. We evaluated the effectiveness and safety of andexanet alfa versus 4F-PCC for management of apixaban- or rivaroxaban-associated intracranial hemorrhage (ICH).. This two-cohort comparison study included andexanet alfa patients enrolled at US hospitals from 4/2015 to 3/2020 in the prospective, single-arm ANNEXA-4 study and a synthetic control arm of 4F-PCC patients admitted within a US healthcare system from 12/2016 to 8/2020. Adults with radiographically confirmed ICH who took their last dose of apixaban or rivaroxaban < 24 h prior to the bleed were included. Patients with a Glasgow Coma Scale (GCS) score < 7, hematoma volume > 60 mL, or planned surgery within 12 h were excluded. Outcomes were hemostatic effectiveness from index to repeat scan, mortality within 30 days, and thrombotic events within five days. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using propensity score-overlap weighted logistic regression.. The study included 107 andexanet alfa (96.6% low dose) and 95 4F-PCC patients (79.3% receiving a 25 unit/kg dose). After propensity score-overlap weighting, mean age was 79 years, GCS was 14, time from initial scan to reversal initiation was 2.3 h, and time from reversal to repeat scan was 12.2 h in both arms. Atrial fibrillation was present in 86% of patients. Most ICHs were single compartment (78%), trauma-related (61%), and involved the intracerebral and/or intraventricular space(s) (53%). ICH size was ≥ 10 mL in volume (intracerebral and/or ventricular) or ≥ 10 mm in thickness (subdural or subarachnoid) in 22% of patients and infratentorial in 15%. Andexanet alfa was associated with greater odds of achieving hemostatic effectiveness (85.8% vs. 68.1%; OR 2.73; 95% CI 1.16-6.42) and decreased odds of mortality (7.9% vs. 19.6%; OR 0.36; 95% CI 0.13-0.98) versus 4F-PCC. Two thrombotic events occurred with andexanet alfa and none with 4F-PCC.. In this indirect comparison of patients with an apixaban- or rivaroxaban-associated ICH, andexanet alfa was associated with better hemostatic effectiveness and improved survival compared to 4F-PCC. Trial registration NCT02329327; registration date: December 31, 2014.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Factors; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Intracranial Hemorrhages; Propensity Score; Prospective Studies; Pyrazoles; Pyridones; Recombinant Proteins; Retrospective Studies; Rivaroxaban; Thrombosis

Topics: Electrocardiography; Humans; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome; Ventricular Function, Left

Heparin-induced thrombocytopenia (HIT), a potentially devastating form of drug-induced thrombocytopenia, occurs in patients receiving heparin for thrombosis prevention or treatment. An isolated HIT is characterized by decreased platelet counts without thrombosis, which are atypical and difficult to clinically find.. A 33-year-old female patient's admission examination revealed elevated D-dimer levels. After prophylactic anticoagulation using low-molecular weight heparin, her blood platelet counts were rapidly decreased, whereas her D-dimer levels increased, followed by presentations of chest tightness, abdominal pain, and skin itching without thrombosis. After excluding all the other causes of thrombocytopenia, HIT was suspected. Her 4Ts score was 5 points, and enzyme-linked immunoassay for platelet factor 4 (PF4)/heparin antibodies was positive, indicating isolated HIT.. The patient was diagnosed with advanced lung cancer presenting with isolated HIT. We immediately stopped low-molecular weight heparin and initiated rivaroxaban for anticoagulation. We administered thrombopoietin (TPO) and avatripopal maleate tablets to increase blood platelet counts, whereas intravenous immunoglobulin (IVIG) was administered to stimulate her immune system. The patient's thrombocytopenia was successfully treated without thrombosis and bleeding complications.. Rivaroxaban is a potential option for tumor preventive anticoagulation and HIT treatment. Early HIT identification is necessary. After identification, the 4Ts score as well as PF4/heparin antibodies should be assessed and appropriate anticoagulants selected based on patients' conditions.

Topics: Adult; Antibodies; Anticoagulants; Female; Heparin; Humans; Lung Neoplasms; Platelet Factor 4; Rivaroxaban; Thrombocytopenia; Thrombosis

This is the first study examining real-life data of pediatric cancer patients treated with rivaroxaban. Children with thrombocytopenia and high bleeding risk were excluded from previous clinical trials. Data regarding the safety and efficacy of rivaroxaban in pediatric cancer-associated thrombosis are scarce. Our case series included 16 children aged 7.5-17 years. Thrombus resolution rate in our study was comparable to results of previous studies. However, higher rates of thrombotic and bleeding complications were seen in our study as compared to previous reports, especially among patients with relapsed or refractory disease.

Topics: Anticoagulants; Child; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Thrombosis; Treatment Outcome; Venous Thromboembolism

Some patients with atrial fibrillation (AF) develop left atrial appendage thrombus (LAAT) despite receiving anticoagulant treatment. Different scores were proposed to evaluate thromboembolic risk in patients with AF. Risk stratification according to sex is common in clinical practice.. We aimed to identify predictors of LAAT separately in men and women treated with dabigatran or rivaroxaban.. This retrospective study included 1256 patients (479 women [38.1%]) with AF who underwent transesophageal echocardiography before electrical cardioversion or catheter ablation, between January 2013 and December 2019, and received dabigatran or rivaroxaban for at least 3 weeks.. Multivariable logistic regression analysis revealed nonparoxysmal AF to predict LAAT in women (odds ratio [OR], 9.70; P = 0.002). In men, the predictors were heart failure (OR, 4.14; P = 0.001), diabetes (OR, 2.64; P = 0.002), nonparoxysmal AF (OR, 5.61; P = 0.02), and estimated glomerular filtration rate below 60 ml/min/1.73 m2 (OR, 2.77; P = 0.01). In the receiver operating characteristic curve analysis, the CHA2DS2‑VASc-RAF score had the highest value for predicting LAAT in women (area under the curve [AUC] = 0.786). In men, CHA2DS2‑VASc-RAF, CHA2DS2, CHA2DS2‑VASc, and R2CHADS2 had sufficient predictive value (AUC = 0.786, 0.726, 0.734, and 0.780, respectively).. The predictors of LAAT differ between men and women treated with dabigatran or rivaroxaban. In women, the CHA2DS2‑VASc‑RAF score had the highest predictive value, while in men all the scores had equally sufficient predictive value.

Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Dabigatran; Female; Heart Diseases; Humans; Male; Retrospective Studies; Rivaroxaban; Thrombosis

Non-retrieved inferior vena cava filter (IVCF) is associated with some severe complications, such as filter thrombosis. The aim of this retrospective cohort study was to evaluate the outcome of rivaroxaban for the prevention of filter thrombosis in patients with non-retrieved IVCF.. The study based on the VTE registry databases was limited to patients with non-retrieved IVCF treated at Nanjing Drum Tower Hospital from January 2012 to December 2017. Outcomes included filter thrombosis, total bleeding events, death.. A total of 202 patients were enrolled in the study and divided into rivaroxaban group and warfarin group. Mean follow-up period of the two groups was 57.4 ± 20.8 and 62.2 ± 23.0 months, respectively. In risk factors for VTE, transient factors (P = 0.008) and history of VTE (P = 0.028) were statistically different between the two groups. A total of 13 (6.4%) patients developed filter complications, of which 4 (3.5%) and 5 (5.7%) patients in rivaroxaban group and warfarin group developed filter thrombosis, respectively, without significant difference (P = 0.690). The total bleeding events in rivaroxaban group, including major bleeding and clinically relevant and non-major (CRNM) bleeding, were significantly lower than that in warfarin group (P = 0.005). Adjusting for hypertension, transient risk factors, history of VTE and cancer, no differences in the hazard ratio for outcomes were notable.. It is necessary to perform a concomitant anticoagulation in patients with non-retrieved filters. Rivaroxaban can be an alternative anticoagulant option for the prevention of filter thrombosis.

Topics: Anticoagulants; Humans; Retrospective Studies; Rivaroxaban; Thrombosis; Vena Cava Filters; Venous Thromboembolism; Warfarin

Historically, treatment of heparin-induced thrombocytopenia (HIT) includes a non-heparin parenteral anticoagulant with bridging to warfarin once platelets recover. Data supporting the use of direct oral anticoagulants (DOACs) for HIT treatment are limited. Given the paucity of evidence for the use of DOACs in HIT, the aim of this study is to describe the prescribing patterns of DOACs for HIT at our institution. This is a single center, retrospective chart evaluation of patients admitted from January 2017 to October 2020 with a confirmed diagnosis of HIT. Twenty-six patients were identified; 21 patients (81%) received initial parenteral treatment and 5 patients (19.2%) with initial DOAC treatment. The most frequently used DOAC was apixaban at the VTE treatment dose [15 (57.7%)] followed by the reduced dose of apixaban [5 (19.2%)]. Of the patients initially treated with a parenteral agent, 11 (42.3%) were transitioned to a DOAC after platelet recovery, 7 (26.9%) transitioned as platelets were steadily increasing, and 3 (11.5%) transitioned at the time of discharge (prior to platelet recovery). Platelet recovery was achieved in 23 patients (88.5%) at a median of 5 days (IQR 2.8-8.3) after HIT diagnosis. No new thrombotic or bleeding events occurred within 30 days of HIT diagnosis. In our patients treated with a DOAC for HIT, no progression of HIT was observed. Apixaban was the most frequently utilized DOAC. Most patients received a parenteral anticoagulant prior to DOAC initiation. All patients managed with a DOAC as initial treatment achieved platelet recovery within 30 days of HIT diagnosis.

Topics: Administration, Oral; Anticoagulants; Humans; Retrospective Studies; Rivaroxaban; Thrombocytopenia; Thrombosis; Warfarin

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

Rivaroxaban, a direct oral anticoagulant, is effective against venous thromboembolism (VTE) recurrence without increasing the risk of major bleeding in patients with cancer-associated venous thromboembolism (CAT). However, its clot regression effects are poorly understood. This single-arm, prospective interventional study aimed to investigate the clot regression effects of rivaroxaban in 40 CAT patients, through a contrast-enhanced computed tomography at baseline, 3 weeks, and 3 months of rivaroxaban treatment. The primary endpoint was the clot-regression ratio calculated from the thrombus volumes at 3 weeks and 3 months. Compared with baseline, the total clot volume was significantly reduced at both 3 weeks and 3 months after initiation (p < 0.01). The clot-regression rates were statistically significant with 83.1% (95% confidence interval [CI], 73.8-92.3%) at 3 weeks and 98.7% (95% CI, 97.1-100.2%) at 3 months, with complete resolution in 36.1% and 80.8% of patients at 3 weeks and 3 months, respectively. One patient had recurrent VTE after dose reduction, and seven had non-fatal major bleeding. Therefore, rivaroxaban had a sufficient clot-regression effect against CAT with caution of bleeding complication.

Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Prospective Studies; Rivaroxaban; Thrombosis; Venous Thromboembolism

Atherosclerotic cardiovascular disease (ASCVD), which includes coronary artery disease (CAD), cerebrovascular disease, and peripheral arterial disease (PAD) is associated with significant morbidity, mortality, and healthcare costs. Antiplatelet therapy has long been the mainstay of antithrombotic therapy for the prevention of first-ever and recurrent ASCVD events. More recently, however, randomized trials have demonstrated the benefits and cost-effectiveness of a dual pathway inhibition (DPI) strategy in acute and chronic ASCVD. When used in combination, aspirin and low-dose rivaroxaban work synergistically to inhibit platelet activation and thrombin generation, thereby preventing thrombus formation. Among patients with recent acute coronary syndrome (ACS), those with positive cardiac biomarkers or ST-segment elevation myocardial infarction, or a history of heart failure derive the greatest absolute benefits. Among patients with chronic ASCVD, those with involvement of two or more vascular beds, heart failure, chronic kidney disease, or diabetes derive the greatest absolute benefits. Additional trials are underway to assess the impact of DPI therapy in other populations of interest, including patients with ACS at high risk of left ventricular thrombus formation, intracranial atherosclerotic disease with recent transient ischemic attack or stroke, peripheral arterial disease with limiting claudication or post lower extremity revascularization, and advanced chronic kidney disease with ASCVD or risk factors for ASCVD. Further work is required to assess the possible added benefit of combining rivaroxaban with clopidogrel or ticagrelor instead of aspirin.

Topics: Acute Coronary Syndrome; Aspirin; Atherosclerosis; Cardiovascular Diseases; Drug Therapy, Combination; Heart Failure; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Rivaroxaban; Thrombosis

Although not routinely recommended, anti-Xa level monitoring for apixaban or rivaroxaban may be useful in certain clinical scenarios. There are currently no laboratory standards, therapeutic ranges, or proven correlation between anti-Xa levels and clinical outcomes.. This study describes the utilization, application, and association of anti-Xa levels with clinical outcomes in patients receiving apixaban or rivaroxaban.. This retrospective, descriptive study included adult inpatients within the Houston Methodist System on apixaban or rivaroxaban with at least one anti-Xa level ordered subsequent to administered doses. The primary endpoint was major bleeding according to International Society on Thrombosis and Haemostasis criteria. Secondary endpoints included reasons for anti-Xa level ordering, anti-Xa levels at different time intervals post-dose, and thrombotic events. Pre-specified subgroup analyses were performed to further evaluate the primary endpoint.. The study population consisted of 169 patients and 234 anti-Xa levels. Twenty-nine levels were obtained in context of major bleeding. The majority of levels were not drawn as peak levels 2-4 hours post-dose, however remained quantifiable above typical observed levels within this timeframe and well beyond 24 hours post-dose. Patient characteristics with major bleeding included elderly age, acute renal impairment, and low body weight. At least 14 unique reasons for anti-Xa level ordering were identified. Twenty-nine levels were associated with thrombotic events.. Anti-Xa levels may be useful for assessment of current drug concentrations, immediate safety of therapy, and guidance for possible clinical interventions. Dose titration and reversal therapies based on anti-Xa level results in major bleeding warrant further research.

Topics: Adult; Aged; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Pyridones; Retrospective Studies; Rivaroxaban; Thrombosis

Left ventricular thrombus (LVT) can complicate ST-Elevation myocardial infarction (STEMI) and is associated with poor outcomes. Conventional triple anticoagulation [Vitamin K Antagonists (VKA) plus dual-antiplatelet therapy (DAPT)] is the first-line therapy for LVT after STEMI. In patients with LVT following STEMI, contemporary data of triple therapy with rivaroxaban are lacking.. We conducted a retrospective cohort study involving 1335 STEMI patients who underwent primary percutaneous coronary intervention (PCI). Among patients who developed LVT after STEMI, we observed differences in efficacy between rivaroxaban plus DAPT therapy and VKA plus DAPT. The time of LVT resolution was also evaluated, as well as net clinical adverse events, and rates of bleeding events.. In 1335 patients with STEMI, a total of 77 (5.7%) developed LVT over the follow-up period (median 25.0 months). Of the patients diagnosed with LVT, 31 patients were started on triple therapy with VKA, 33 patients on triple therapy with rivaroxaban. There was a consistent similarity in LVT resolution with rivaroxaban application compared to VKA application during the follow-up period [HR (log-rank test) 1.57(95% CI 0.89-2.77), p = 0.096; Adjusted HR 1.70(95% CI 0.90-3.22), p = 0.104]. Triple therapy with rivaroxaban showed quicker resolution than with VKA (6 months: p = 0.049; 12 months: p = 0.044; 18 months: p = 0.045). Similar risks of ISTH bleeding were not significantly different between the 2 groups [VKA 9.7% vs Rivaroxaban 6.1%, Adjusted HR 0.48 (95% CI 0.73-3.20); p = 0.444)]. Fewer net adverse clinical events (NACE) were observed in the rivaroxaban group [VKA 58.1% vs Rivaroxaban 24.2%; HR (log-rank test) 0.31(95% CI 0.14-0.68), p = 0.003; Adjusted HR 0.23(95% CI 0.09-0.57), p = 0.001].. In the observational study, triple therapy with rivaroxaban has similar and quicker LVT resolution in patients with LVT after STEMI, compared with triple therapy with VKA, and perhaps was associated with a better clinical benefit. Larger sample sizes and randomized controlled trials are needed to confirm this observation.

Topics: Anticoagulants; Humans; Percutaneous Coronary Intervention; Retrospective Studies; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome; Vitamin K; Warfarin

It is unclear whether elderly patients established on direct oral anticoagulants (DOACs) have greater exposure to these drugs, which could subsequently increase their risk of bleeding. We assessed DOAC exposure and factors affecting it in a real-world elderly cohort of patients. For this, 151 medically stable hospital inpatients (76 established on apixaban, 61 on rivaroxaban, 14 on dabigatran) with a median [interquartile range (IQR)] age of 84 (78-89) years were recruited. Patients provided blood samples for measurement of peak and trough plasma DOAC concentrations. There was up to 48-fold and 13-fold variation in trough and peak plasma drug concentrations respectively. A significantly greater proportion of patients on apixaban had peak plasma drug concentrations within the reported ranges compared to those on either rivaroxaban or dabigatran (82·9% vs. 44·3% vs. 64·3% respectively; P < 0·001). A third of the variability in DOAC plasma concentrations was attributed to the influences of DOAC dosage, renal function and gender. To what extent the observed increases in DOAC exposure in the older patients is the cause of their increased risk of bleeding, which could potentially be ameliorated by dosing titration, requires further investigation.

Topics: Age Factors; Aged; Aged, 80 and over; Dabigatran; Drug Monitoring; Factor Xa Inhibitors; Female; Hospitalization; Humans; Male; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Male; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Thrombosis

Atrial fibrillation (AF) is associated with increased risk of stroke and thromboembolism. Patients with AF have a higher incidence of renal impairment, which may influence the risks of systemic thromboembolism or bleeding. We determined how different oral anticoagulants affect plasma clot properties and whether progressive renal dysfunction affects plasma clot properties in patients on warfarin.. We studied 257 patients with AF receiving oral anticoagulants. Furthermore, we recruited 192 separate patients with AF on warfarin and divided them in 4 groups based on estimated glomerular filtration rate (eGFR). Platelet poor plasma was prepared and clot formation and fibrinolysis was monitored kinetically up to 1 h.. Rate of clot formation was significantly slower with dabigatran and rivaroxaban. Time between 50% clotting and 50% lysis was prolonged in patients receiving warfarin compared to NOACs. Time to 50% lysis from maximum absorbance was significantly shorter in patients receiving rivaroxaban. Time between 50% clotting and 50% lysis became significantly prolonged with worsening eGFR. Time to 50% lysis from maximum absorbance was prolonged as renal function worsened.. Compared to warfarin, NOACs differently modulate coagulation and fibrinolysis under ex vivo conditions. Worsening renal function in AF patients on warfarin prolongs fibrinolysis, potentially increasing the risk of thrombosis.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pyridones; Rivaroxaban; Stroke; Thrombosis; Warfarin

Topics: Antiphospholipid Syndrome; Blood Coagulation; Factor Xa Inhibitors; Humans; Retrospective Studies; Rivaroxaban; Thrombosis; Treatment Outcome

Thromboembolic events remain clinically unresolved after transcatheter aortic valve implantation (TAVI). The use of direct oral anticoagulant (DOAC) to reduce thrombosis associated with TAVI remains controversial. This study aimed at investigating the periprocedural change in blood coagulation and thrombolysis parameters in 199 patients undergoing transfemoral TAVI. Prothrombin activation fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), soluble fibrin monomer complex (SFMC), and fibrin/fibrinogen degradation product (FDP) levels were measured before and 1 hour after TAVI and 1, 2, and 7 days postoperatively. Of the 199 patients, 49 were treated with DOAC (apixaban in 32, edoxaban in 10, and rivaroxaban in 7). The F1 + 2 and TAT levels immediately increased 1 hour after TAVI and then gradually decreased in both groups. The SFMC level also significantly increased with a peak on day 1. The FDP level gradually increased, peaking on day 2. The values of F1 + 2, TAT, SFMC, and FDP in patients who used DOAC were significantly lower than those who did not use DOAC at 1 hour after TAVI in F1 + 2 (600 [452 to 765] vs 1055 [812 to 1340] pmol/L; p < 0.001), TAT (21.4 [16.2 to 37.0] vs 38.7 [26.4 to 58.7] μg/mL; p < 0.001) and on day 1 in SFMC (18.2 [9.4 to 57.9] vs 113.4 [70.9 to 157.3] μg/mL; p < 0.001) and day 2 in FDP (6.0 [4.7 to 10.0] vs 12.6 [8.2 to 17.4] μg/mL; p < 0.001). Ischemic stroke within 30 days after TAVI occurred in 3 patients (1.5%), who were not treated with DOAC. Coagulation cascade activation was observed after TAVI. DOAC could reduce transient hypercoagulation following TAVI.

Topics: Aged, 80 and over; Antithrombin III; Aortic Valve Stenosis; Blood Coagulation; Cohort Studies; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Peptide Fragments; Peptide Hydrolases; Prothrombin; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Transcatheter Aortic Valve Replacement

Topics: Antifibrinolytic Agents; Humans; Prospective Studies; Rivaroxaban; Thrombosis; Tranexamic Acid

Current guidelines recommend anticoagulation as the mainstay of portal vein thrombosis (PVT) treatment in cirrhosis. However, because of the heterogeneity of PVT, anticoagulation alone does not always achieve satisfactory results. This study aimed to prospectively evaluate an individualized management algorithm using a wait-and-see strategy (i.e., no treatment), anticoagulation, and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT in cirrhosis.. Between February 2014 and June 2018, 396 consecutive patients with cirrhosis with nonmalignant PVT were prospectively included in a tertiary care center, of which 48 patients (12.1%) were untreated, 63 patients (15.9%) underwent anticoagulation, 88 patients (22.2%) underwent TIPS, and 197 patients (49.8%) received TIPS plus post-TIPS anticoagulation. The decision of treatment option mainly depends on the stage of liver disease (symptomatic portal hypertension or not) and degree and extension of thrombus.. During a median 31.7 months of follow-up period, 312 patients (81.3%) achieved partial (n = 25) or complete (n = 287) recanalization, with 9 (3.1%) having rethrombosis, 64 patients (16.2%) developed major bleeding (anticoagulation-related bleeding in 7 [1.8%]), 88 patients (22.2%) developed overt hepatic encephalopathy, and 100 patients (25.3%) died. In multivariate competing risk regression models, TIPS and anticoagulation were associated with a higher probability of recanalization. Long-term anticoagulation using enoxaparin or rivaroxaban rather than warfarin was associated with a decreased risk of rethrombosis and an improved survival, without increasing the risk of bleeding. However, the presence of complete superior mesenteric vein thrombosis was associated with a lower recanalization rate, increased risk of major bleeding, and poor prognosis.. In patients with cirrhosis with PVT, the individualized treatment algorithm achieves a high-probability recanalization, with low rates of portal hypertensive complications and adverse events.

Topics: Adult; Aged; Algorithms; Anticoagulants; Combined Modality Therapy; Enoxaparin; Female; Hemorrhage; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Male; Middle Aged; Mortality; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Prospective Studies; Recurrence; Rivaroxaban; Severity of Illness Index; Thrombosis; Warfarin; Watchful Waiting

Topics: Antifibrinolytic Agents; Humans; Prospective Studies; Rivaroxaban; Thrombosis; Tranexamic Acid

To evaluate the current interpretation of the lower doses of direct oral anticoagulants (DOAC) dabigatran, apixaban, edoxaban and rivaroxaban in nonvalvular atrial fibrillation.. A questionnaire of 14 statements to which the possible answers were fully agree/partially agree/partially disagree/fully disagree or yes/no was prepared within the board of the Italian Atherosclerosis, Thrombosis and Vascular Biology Study Group and forwarded to individual Italian physicians.. A total of 620 complete questionnaires were received from nearly all the Italian regions and physicians of various medical specialists, either enabled or not for the prescription of DOAC. A wide agreement was found as regards the pharmacological, as well as clinical consequences of the administration of the lower dose of factor-Xa inhibitors both in patients with and without clinical and/or laboratory criteria requiring dose reduction. Wide agreement was also found as regards the presence of moderate kidney insufficiency in selecting the dose of DOAC. Instead, more debated were issues regarding the proportionality between dabigatran dose and plasma concentration and selection of dabigatran dose, as well as the role of measuring drug plasma concentration and/or determine the anticoagulant activity of factor-Xa inhibitors when used at the lower dose.. The interpretation of the lower doses of DOAC in current Italian clinical practice appears largely correct and shared. Because of the persistence of some residual uncertainties, essentially regarding dabigatran, however, continuous educational effort still appears warranted.

Topics: Administration, Oral; Anticoagulants; Atherosclerosis; Atrial Fibrillation; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Humans; Italy; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Rivaroxaban; Surveys and Questionnaires; Thiazoles; Thrombosis; Treatment Outcome

Atorvastatin and direct oral factor Xa inhibitors (xabans) are frequently co-administrated in patients with atrial fibrillation (AF). However, no studies investigating the possibility of the pharmacologic interaction between these agents have been conducted. The aim of this prospective observational study was to determine the impact of atorvastatin therapy on anti-Xa activity in xabans-treated patients with AF. We enrolled 115 AF patients on long-term rivaroxaban (52 patients) and long-term apixaban (63 patients) therapy. Long-term atorvastatin (40 mg once daily) was administrated to 28 rivaroxaban-treated patients and to 28 apixaban-treated patients. Trough and peak samples were tested for anti-Xa activity with drug-specific anti-Xa chromogenic analysis. For rivaroxaban, there were no significant differences in trough activity (45.5 ± 39.5 ng/ml vs. 46.2 ± 30.1 ng/ml; p = .34) and peak anti-Xa activity (179.2 ± 108.8 ng/ml vs. 208.1 ± 104.1 ng/ml; p = .94) between atorvastatin-treated patients and those without atorvastatin. Similarly, atorvastatin did not impact the trough activity (127.7 ± 71.1 ng/ml vs. 100.8 ± 61.1 ng/ml; p = .12) or peak anti-Xa activity (213.8 ± 103.6 ng/ml vs. 179.3 ± 72.9 ng/ml; p = .14) among apixaban-treated patients with AF. This observational study did not show a significant impact of atorvastatin on trough and peak anti-Xa activity in xabans-treated patients with AF.

Topics: Aged; Aged, 80 and over; Atorvastatin; Atrial Fibrillation; Drug Interactions; Factor Xa Inhibitors; Female; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thrombosis

Cytomegalovirus (CMV) is reported to have thrombogenic characteristics that activate factor X in vitro and stimulate the production of factor VIII and von Willebrand factor (vWF). Thrombosis associated with CMV infection is prevalent among immunocompromised patients and predominantly presents as a solitary large thrombus in the deep vein, pulmonary artery, splanchnic arteriovenous ducts, or other similar sites. Multiple thrombi, however, are rarely observed in such cases. Here, we report about an immunocompetent man with multiple microthrombi associated with CMV infection.. A 72-year-old Japanese man who complained of abdominal pain was hospitalized with multiple colonic stenosis. He was later diagnosed with CMV enterocolitis and treated with ganciclover from Day 27 post-admission. During hospitalization, the patient developed thrombi in his fingers. He was initially treated with anticoagulant therapy (rivaroxaban); however, the therapy was discontinued owing to a prolonged activated thromboplastin time and an elevated international normalized ratio of prothrombin time. Instead, vitamin K and fresh-frozen plasma were administered. Nevertheless, his coagulation profile remained abnormal. Eventually, he developed colonic perforation and had to undergo emergency surgery. An intraoperative specimen showed several microthrombi in the middle and small arteriovenous ducts of his small and large intestines. The patient's coagulopathy improved preoperatively, and his overall condition improved postoperatively. Since the activation of ADAMTS13 was reduced remarkably, the thrombotic tendency was determined to be a thrombotic microangiopathy-like condition owing to increased vWF. We could not attribute the coagulopathy to any other cause except CMV infection; therefore, we concluded that this was a case of multiple thrombosis associated with CMV.. We present an extremely rare case of a patient with multiple thrombotic microangiopathy-like microthrombosis caused by CMV infection. Our findings suggest that CMV infection may be considered as a differential diagnosis for immunocompetent individuals who present with thrombosis of unspecified cause.

Topics: ADAMTS13 Protein; Aged; Anticoagulants; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Enterocolitis; Ganciclovir; Humans; Intestinal Perforation; Male; Rivaroxaban; Serologic Tests; Thrombosis

Topics: Antifibrinolytic Agents; Humans; Prospective Studies; Rivaroxaban; Thrombosis; Tranexamic Acid

BACKGROUND Left ventricular thrombus (LVT) is a complication of left ventricular dysfunction and myocardial infarction (MI) and is associated with systemic thromboembolism. Two-dimensional transthoracic echocardiography (TTE) is considered the first-line diagnostic tool for detection of LVT. Vitamin K antagonists (VKA) targeting an international normalized ratio (INR) from 2 to 3 are the only approved treatments by the Food and Drug Administration (FDA). New emerging observational data support the use of direct oral anticoagulants (DOACs) as an alternative therapeutic option; however, their safety and efficacy have not been assessed in a good-quality randomized controlled trial. CASE REPORT Here, we present a case of a 43-year-old man diagnosed with human immunodeficiency virus (HIV)-associated dilated cardiomyopathy complicated with an LVT. He was treated with rivaroxaban for 9 consecutive months with no interruption of therapy at any point in time; however, he presented to the emergency department with symptoms of decompensated heart failure. A follow-up TTE demonstrated a significant increase in the size of his LVT. This case questions the efficacy of using factor Xa inhibitor (rivaroxaban) as an alternative option for LVT treatment. CONCLUSIONS This case demonstrates a failure of rivaroxaban in treating LVT in a patient with HIV-associated dilated cardiomyopathy. Good-quality randomized clinical trials or prospective studies are required to establish the efficacy and safety of DOACs for LVT treatment as an alternative to VKA.

Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Humans; Male; Prospective Studies; Rivaroxaban; Thrombosis

There are scarce data evaluating the effectiveness and safety of rivaroxaban vs. warfarin in non-valvular atrial fibrillation (NVAF) patients with concomitant coronary artery disease (CAD) and/or peripheral artery disease (PAD) treated in routine practice.. Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant (OAC)-naïve NVAF patients receiving rivaroxaban (15-20 mg once daily) or warfarin, with comorbid CAD and/or PAD and ≥12 months of insurance coverage before OAC initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores (standardized differences <0.1 achieved for all covariates after adjustment). Endpoints included a composite of major thrombotic vascular events (MTVEs) (including ischaemic stroke, myocardial infarction, or need for lower limb revascularization/major amputation) and major bleeding. Patients were followed until an event-of-interest, discontinuation/switch of index OAC, insurance disenrolment, or end-of-data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. We identified 3257 rivaroxaban (30.4% received a 15 mg dose) and 5046 warfarin users with NVAF and comorbid CAD and/or PAD. Rivaroxaban was associated with a 32% (95% CI = 8-50%) reduction in the composite of MTVE. No significant difference in major bleeding was observed (HR = 1.13, 95% CI = 0.84-1.52). No statistical interactions were noted in subgroup analyses performed on the MTVE (P-interaction ≥ 0.35 for all) or major bleeding endpoints (P-interaction ≥ 0.09 for all).. Among patients with NVAF and comorbid CAD and/or PAD, rivaroxaban use was associated with a reduced risk of MTVEs vs. warfarin, without significantly increasing major bleeding risk.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Coronary Artery Disease; Databases, Factual; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Thrombosis; Time Factors; Treatment Outcome; United States; Warfarin

Patients treated with direct Xa inhibitors may require urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is common; however, it is based on limited experience in healthy volunteers.. To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery and evaluate its efficacy and safety.. This was a retrospective study in 2 tertiary hospitals. Bleeding was evaluated based on surgical reports, hemoglobin drop, and the use of blood products or additional PCC during 48 h. Safety measures were thrombotic complications and 30-day mortality.. Sixty-two patients aged 80.7 ± 9 years, treated with apixaban (39.63%) or rivaroxaban (23.37%), received PCC before an urgent surgery/procedure. Most underwent abdominal operation (61%), orthopedic surgery (13%), or transhepatic cholecystostomy insertion (10%). Bleeding during surgery was reported in 3 patients (5%), no patient required additional PCC, and 16 patients (26%) received packed cells (median: 1 unit, range: 1-5). The 30-day mortality and thrombosis rates were 21% (n = 13) and 3% (n = 2), respectively. The cause of death was related to the primary disease, most commonly sepsis. No patient died due to bleeding/thrombosis.. Our results support the use of PCC to achieve hemostasis in patients treated with Xa inhibitors prior to an urgent surgery.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Atrial Fibrillation; Blood Coagulation Factors; Blood Component Transfusion; Blood Loss, Surgical; Emergencies; Factor Xa Inhibitors; Female; Hemostatics; Humans; Male; Postoperative Hemorrhage; Preoperative Care; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Surgical Procedures, Operative; Tertiary Care Centers; Thrombophilia; Thrombosis; Tranexamic Acid

Clinical experience with using activated prothrombin complex concentrates (aPCCs) to reverse the effects of factor Xa inhibitors is limited.. Our objective was to assess the achievement of effective clinical hemostasis using aPCC in patients on chronic apixaban or rivaroxaban therapy presenting with major bleeding in whom a reversal agent is warranted. We also assessed the safety of the drug.. A retrospective medical records review was conducted at a tertiary referral medical center in the USA. Patients presenting with major bleeding while receiving apixaban or rivaroxaban and treated with aPCC were included. Clinical hemostasis was assessed using International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria.. A total of 35 patients were included in the study. The most common site of bleeding was intracerebral hemorrhage (ICH) (n = 18 [51.4%]), followed by gastrointestinal bleed (n = 10 [28.6%]). Clinical hemostasis was achieved in 24 (68.6%) patients; 11 patients (31.4%) did not achieve clinical hemostasis; nine of these patients had ICH. Seven of the patients who did not achieve hemostasis died during hospitalization. Three (8.6%) patients experienced thromboembolic events during hospitalization. In total, 21 (60%) patients were receiving concomitant medications that interact with anti-factor Xa inhibitors and can increase the risk of bleeding.. Our study suggests that aPCC could be an option in patients with major bleeding associated with apixaban or rivaroxaban. It may be an alternative for patients who need anticoagulation reversal if the specific antidote, andexanet alfa, is unavailable.

Topics: Aged; Antidotes; Blood Coagulation; Blood Coagulation Factors; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Hemostasis; Humans; Intracranial Hemorrhages; Male; Outcome and Process Assessment, Health Care; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Survival Analysis; Thrombosis; United States

A reduced rate of myocardial infarction has been reported in patients with atrial fibrillation treated with FXa (factor Xa) inhibitors including rivaroxaban compared with vitamin K antagonists. At the same time, low-dose rivaroxaban has been shown to reduce mortality and atherothrombotic events in patients with coronary artery disease. Yet, the mechanisms underlying this reduction remain unknown.. In this study, we hypothesized that rivaroxaban's antithrombotic potential is linked to a hitherto unknown rivaroxaban effect that impacts on platelet reactivity and arterial thrombosis.. In this study, we identified FXa as potent, direct agonist of the PAR-1 (protease-activated receptor 1), leading to platelet activation and thrombus formation, which can be inhibited by rivaroxaban. We found that rivaroxaban reduced arterial thrombus stability in a mouse model of arterial thrombosis using intravital microscopy. For in vitro studies, atrial fibrillation patients on permanent rivaroxaban treatment for stroke prevention, respective controls, and patients with new-onset atrial fibrillation before and after first intake of rivaroxaban (time series analysis) were recruited. Platelet aggregation responses, as well as thrombus formation under arterial flow conditions on collagen and atherosclerotic plaque material, were attenuated by rivaroxaban. We show that rivaroxaban's antiplatelet effect is plasma dependent but independent of thrombin and rivaroxaban's anticoagulatory capacity.. Here, we identified FXa as potent platelet agonist that acts through PAR-1. Therefore, rivaroxaban exerts an antiplatelet effect that together with its well-known potent anticoagulatory capacity might lead to reduced frequency of atherothrombotic events and improved outcome in patients.

Topics: Animals; Arteries; Blood Platelets; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Mice, Inbred C57BL; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Receptor, PAR-1; Rivaroxaban; Thrombosis

Patients with mechanical heart valves (MHVs) require warfarin to prevent thromboembolism. Dabigatran was less effective than warfarin in patients with MHVs, which prompted a black box warning against the use of direct oral anticoagulants for this indication. However, rivaroxaban and apixaban, which inhibit factor Xa, have not been evaluated in patients with MHVs. To determine whether rivaroxaban and apixaban would be effective, we used MHV-induced thrombin generation assays to compare them with warfarin either alone or in combination with dabigatran.. Thrombin generation in the absence or presence of MHV leaflets or sewing ring segments (SRSs) was quantified. Studies were done in control plasma; plasma from patients on warfarin; plasma containing varying concentrations of rivaroxaban, apixaban, or dabigatran alone; or plasma containing rivaroxaban plus dabigatran.. Mean endogenous thrombin potential (ETP) increased 1.2-fold, 1.5-fold, and 1.8-fold in the presence of leaflets, Teflon (Terumo Aortic (Sunrise, FL)) SRSs, or Dacron (Terumo Aortic (Sunrise, FL)) SRSs, respectively. Rivaroxaban and apixaban reduced ETP at concentrations above 50 ng/mL but were less effective than warfarin. When rivaroxaban and dabigatran were combined, they suppressed ETP in a more than additive manner.. Whereas warfarin suppresses MHV-induced thrombin generation, MHVs induce the generation of factor Xa in concentrations that overwhelm clinically relevant concentrations of rivaroxaban or apixaban. When used in combination, rivaroxaban and dabigatran are more effective than either agent is alone, suggesting that concomitant inhibition of factor Xa and thrombin is better than inhibition of either clotting enzyme alone.

Topics: Antithrombins; Dabigatran; Factor Xa Inhibitors; Heart Diseases; Heart Valve Prosthesis; Humans; Rivaroxaban; Thrombin; Thrombosis

Data comparing dabigatran with rivaroxaban regarding the resolution of left atrial/left atrial appendage (LA/LAA) thrombus in patients with nonvalvular atrial fibrillation (AF) are scarce. This study aimed to compare the efficacy and safety of dabigatran vs rivaroxaban regarding the resolution of LA/LAA thrombus in patients with nonvalvular AF.. This retrospective study enrolled nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2014 and January 2019. Altogether, 34 patients with LA/LAA thrombus detected by transesophageal echocardiography (TEE) were enrolled. Among them, 12 patients were treated with dabigatran 150 mg bid and the other 22 with rivaroxaban 20 mg qd. Follow-up TEE was performed within greater than or equal to 3 weeks to less than 6 months of the initial TEE to evaluate the resolution of the LA/LAA thrombus.. Baseline patient characteristics were similar in the two groups. Overall, 18 patients (81.8%) in the rivaroxaban group had complete thrombus resolution after 70.3 ± 22.1 treatment days, and 10 patients (83.3%) in the dabigatran group had complete thrombus resolution after 69.3 ± 47.9 treatment days. There was no significant difference between the groups (P = .6). TEE showed that the average length, width, and area of thrombus significantly decreased in both groups after treatment, although there was no significant difference in the amount of change in these parameters between the two groups after treatment (P = .6). Undissolved thrombus in two patients in the rivaroxaban group did dissolve after switching to dabigatran.. The results suggest that both dabigatran and rivaroxaban are potential options for treating LA/LAA thrombus in patients with nonvalvular AF. Dabigatran could be an alternative option for the resolution of LA/LAA thrombus resistant to rivaroxaban.

Topics: Administration, Oral; Aged; Antithrombins; Atrial Appendage; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Thrombosis; Time Factors; Treatment Outcome

Topics: Administration, Oral; Aortic Valve; Aortic Valve Stenosis; Early Termination of Clinical Trials; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Valve Prosthesis; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome

Gigantic left atrium is defined in the current literature as an excessive dilatation of the left atrium above 65mm. Chronic mitral valve disease is associated with the development of thrombus in the left atrium in up to 19% of all cases of mitral insufficiency and appropriate treatment must be initiated to prevent thromboembolic events. In order to diagnose thrombi in the left atrium or left atrial appendage, various imaging methods may be used, including cardiac magnetic resonance.. The case report describes a 73-year-old male who developed recurrent sessile thrombus on the posterior wall of the gigantic left atrium. A large thrombus was first detected following mitral valve surgery despite effective vitamin K antagonist anticoagulation therapy. Echocardiography and cardiac magnetic resonance were used within the diagnostic procedure and to monitor the treatment outcomes. Cardiac magnetic resonance was shown to be beneficial as it provided a more precise description of the intra-atrial masses located on the posterior left atrial wall, and in such situations, is of greater benefit than standard echocardiography. This led to the surgical removal of the intra-atrial mass; nevertheless, it was quickly followed by the recurrence of the thrombus. The anticoagulant therapy was adjusted and fortified by the introduction of acetylsalicylic acid and sequentially clopidogrel, but this also did not resolve the thrombus formation. Finally, employing a combination of rivaroxaban and clopidogrel resulted in partial thrombus regression. Therefore, various pathophysiological aspects of thrombus formation and used anticoagulation strategies are discussed.. We describe a unique case of a recurrent thrombus located on the posterior wall of the gigantic left atrium. Cardiac magnetic resonance was shown to be beneficial in providing a more precise description of the intra-atrial masses located on the posterior left atrial wall as compared to standard echocardiographic examination. Development of a thrombus after mitral valve surgery despite effective anticoagulant therapy and its final resolution by introducing a combination of rivaroxaban and clopidogrel highlights the complex etiopathogenesis of thrombus formation. This supports the potential use of this combination in tailoring an individual personalized therapy for patients with recurrent atrial thrombi.

Topics: Aged; Clopidogrel; Drug Therapy, Combination; Factor Xa Inhibitors; Heart Atria; Heart Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Platelet Aggregation Inhibitors; Recurrence; Rivaroxaban; Thrombectomy; Thrombosis; Treatment Outcome

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

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

The presence of intraluminal thrombus and mitochondrial dysfunction in human abdominal aortic aneurysms (AAAs) have been associated with aneurysmal growth and rupture. The objective of the study was to study if endogenous factor Xa (FXa) may modulate mitochondrial functionality and expression of proteins associated with mitophagy in human AAAs.. AAA sites with intraluminal thrombus were obtained from 6 patients undergoing elective AAA surgery repair. Control samples were collected from 6 organ donors. The effect of FXa was analyzed by in vitro incubation of AAA with 50 nmol/L rivaroxaban, an oral FXa inhibitor.. The enzymatic activities of citrate synthase, a biomarker of mitochondrial density, and cytochrome C oxidase, a biomarker of mitochondrial respiratory chain functionality, were significantly reduced in the AAA sites with respect to the healthy aorta (citrate synthase activity in μU/min/μg protein: control: 3.51 ± 0.22 vs. AAA: 0.37 ± 0.15.; P < 0.01; cytochrome C oxidase activity in μOD/min/μg protein: control: 8.05 ± 1.57 vs. AAA: 3.29 ± 1.05; P < 0.05). The addition of rivaroxaban to AAA reverted the activity of both citrate synthase and cytochrome C oxidase to similar values to control. Mitochondrial Drp-1 expression was higher in AAA sites than in either control aortas or rivaroxaban-incubated AAA sites. Cytosolic content of Drp-1 phosphorylated at Ser637, mitochondrial Parkin, and mitochondrial PINK1-Parkin interaction were significantly reduced in the AAA sites with respect to control aortas. For all these parameters, rivaroxaban-incubated AAA showed similar values compared with control aortas.. In human AAA, rivaroxaban improved mitochondrial functionality that was associated with changes in proteins related to mitophagy. Its opens possible new effects of endogenous FXa on the mitochondria in the human AAA site.

Topics: Adult; Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Case-Control Studies; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Mitochondria; Mitochondrial Proteins; Mitophagy; Rivaroxaban; Thrombosis

Catastrophic antiphospholipid syndrome is the most severe complication of antiphospholipid syndrome. Vitamin K antagonists are the reference treatment for preventing relapsing thrombotic complications in patients with antiphospholipid syndrome. Direct oral anticoagulants are nonetheless sometimes used in this setting. We report two cases of women who were triple-positive for antiphospholipid antibodies and developed catastrophic antiphospholipid syndrome in the week after the introduction of rivaroxaban. The first patient, who had had a previous thrombotic event, had multiorgan failure 3 days after vitamin K antagonists was replaced by rivaroxaban, and the second developed a similar clinical presentation 7 days after introduction of the same treatment. Both catastrophic antiphospholipid syndrome episodes were successfully treated with heparin followed by vitamin K antagonists, corticosteroids, and plasmapheresis. These two cases highlight for the inefficacy of rivaroxaban preventing severe thrombotic events such as catastrophic antiphospholipid syndrome and thus provide further support for recommendations that vitamin K antagonists must remain the reference anticoagulant in patients with triple-positive antiphospholipid antibodies.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Catastrophic Illness; Female; Heparin; Humans; Rivaroxaban; Thrombosis

Topics: Humans; Peptide Hydrolases; Platelet Activation; Receptor, PAR-1; Rivaroxaban; Thrombosis

Topics: Humans; Peptide Hydrolases; Platelet Activation; Receptor, PAR-1; Rivaroxaban; Thrombosis

Congenital protein C deficiency is an important cause of thrombosis in humans but is not described in dogs. A 4-year-old Hungarian Vizsla was presented for investigation of acute onset of ascites. Computed tomography of the chest and abdomen and echocardiography confirmed a large thrombus within the right ventricle. A cause for thrombosis was not initially identified. The clinical signs resolved rapidly and the dog was administered clopidogrel and discharged. Plasma protein C activity measured 2 and 6 weeks later was markedly lower than expected on both occasions. All known causes of acquired protein C deficiency were excluded, and the dog was diagnosed with a congenital protein C deficiency. After diagnosis, the administration of clopidogrel was stopped and administration of rivaroxaban was started. The dog remains well with no evidence of recurrent thrombosis with 6 months of follow-up.

Topics: Animals; Clopidogrel; Dog Diseases; Dogs; Echocardiography; Factor Xa Inhibitors; Male; Platelet Aggregation Inhibitors; Protein C Deficiency; Rivaroxaban; Thrombosis; Tomography, X-Ray Computed

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

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

The stenosis or occlusion of extremities defining peripheral artery disease (PAD) is a risk factor for adverse cardiovascular events and adverse limb events including amputation. PAD is common, can occur without symptoms or with claudication, and is easily diagnosed. Proper diagnosis and adherence to guideline-directed therapy can reduce the morbidity and potential mortality associated with PAD.

Topics: Ankle Brachial Index; Anticholesteremic Agents; Cilostazol; Diet, Healthy; Dual Anti-Platelet Therapy; Endovascular Procedures; Exercise Therapy; Factor Xa Inhibitors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intermittent Claudication; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Smoking Cessation; Thrombosis; Vascular Surgical Procedures; Vasodilator Agents

Topics: Humans; Platelet Activation; Receptor, PAR-1; Rivaroxaban; Thrombosis

Topics: Humans; Platelet Activation; Receptor, PAR-1; Rivaroxaban; Thrombosis

Topics: Anticoagulants; Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; Humans; Neoplasms; Pandemics; Pneumonia, Viral; Rivaroxaban; SARS-CoV-2; Thrombosis; Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) is a high-risk adverse drug reaction because of its associated risk of life- and limb-threatening thrombosis. Rivaroxaban may be considered as an ideal nonheparin anticoagulant alternative for the management of HIT. In this preliminary retrospective study, the efficacy and safety of rivaroxaban to control the clinically suspected HIT (4Ts score 4 points or greater) were evaluated. Patients with chronic kidney disease, hepatic impairment, mechanical heart valves, and active bleeding were excluded. Forty-two eligible patients who received rivaroxaban for clinically suspected HIT were evaluated by medical records review, with 12-month follow-up after the first dose of rivaroxaban. End points included confirmed thrombosis (primary end point), mortality, and adverse treatment-related events. HIT-associated thrombosis was found in 17/42 (40.5%) patients before receiving rivaroxaban. After rivaroxaban therapy, platelet counts normalized in all patients, with only 1/42 (2.3%) patients developing new thrombosis. No hemorrhagic event was recorded in the patients. Twelve patients (28.6%) died, but the cause of death was not related to the thrombosis, hemorrhage, or adverse effects of rivaroxaban. Our findings are consistent with the available emerging data, suggesting that rivaroxaban is a safe and effective drug for the management of clinically suspected HIT. Rivaroxaban is a particularly valuable treatment option in developing countries, where there are issues of cost and availability of approved alternative agents.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Platelets; Complementary Therapies; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Heparin; Humans; Male; Middle Aged; Platelet Count; Retrospective Studies; Rivaroxaban; Thrombocytopenia; Thrombosis; Treatment Outcome

BACKGROUND Transient atrial fibrillation (AF) following percutaneous patent foramen ovale (PFO) closure is common. Anticoagulation therapy should be considered in selected cases of prolonged AF after PFO closure, but guidelines do not provide clear recommendations on indication or choice of anticoagulant therapy for patients with post-procedural AF. CASE REPORT A 45-year-old woman presented with cryptogenic stroke verified by magnetic resonance imaging (MRI). Echocardiography revealed a PFO, which was closed percutaneously using a Gore septal occluder (25 mm). She was discharged on aspirin monotherapy (75 mg oral daily) according to institutional standard. Three weeks later, she presented with atrial fibrillation (AF). A direct oral anticoagulant (DOAC) (rivaroxaban 20 mg once daily) was initiated and aspirin was discontinued. After 4 months of follow-up, a routine echocardiography revealed large thrombi attached to both sides of the PFO occluder. CONCLUSIONS DOACs may be ineffective in preventing thrombus formation on device surfaces. Until more evidence has been provided, we suggest that DOACs are not routinely used for stroke prevention in patients following PFO closure or similar procedures within the first 3 months after device implantation.

Topics: Echocardiography; Factor Xa Inhibitors; Female; Foramen Ovale, Patent; Humans; Middle Aged; Rivaroxaban; Septal Occluder Device; Thrombosis

Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75-100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown.. To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry.. From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion.. Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3-15.8], and serious bleeding was 2.5% at 4 years [1.6-3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9-26.1] vs. 11.6% [9.1-14.8] vs 13.2% [9.2-18.8], P<0.0001, respectively).. The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events.

Topics: Aged; Analysis of Variance; Anticoagulants; Aspirin; Atherosclerosis; Coronary Artery Disease; Drug Administration Schedule; Female; Follow-Up Studies; France; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Patient Selection; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Factors; Rivaroxaban; Stroke; Thrombosis; Time Factors; Treatment Outcome

The attractiveness of direct oral anticoagulants (DOACs) over vitamin K antagonists, in addition to a better benefit-risk ratio, stems from the fact that no therapeutic drug monitoring is deemed necessary. This has been recently mitigated by the fact that increased dabigatran (D) plasma levels have been associated with hemorrhages, and is currently under scrutiny of the European Medicines Agency. We aimed to evaluate, in real conditions of use, whether patients with out-of-range DOAC blood concentrations (too high or too low) were associated with bleeding or thrombosis. Patients treated with D or rivaroxaban (R) were prospectively included in a hospital cohort. D and R plasma levels were measured by high-pressure liquid chromatography-tandem mass spectrometry-at the physician's demand. We defined concentration range as "expected" within the 95% confidence interval of the mean concentration obtained from pivotal trials, and "out of range" when concentrations were outside of that interval. A blind assessment of concentrations versus occurrence of bleeding or thrombosis was performed by means of univariate and multivariate analysis. Three hundred and twenty-two patients (mean age 78.5 years ± 13.1), treated with D or R were included consecutively. They had a mean CHA2DS2-VASc at 4.4 ± 1.7 and a mean HAS-BLED score at 1.7 ± 0.9. Irrespective of the DOAC prescribed, patients presenting with out-of-range concentrations had significantly more bleeding or thrombosis than patients with expected concentrations (P < 0.001). Patients with bleeding were more prone to have concentrations beyond the 95 percentile (N = 62, P < 0.001), whereas patients with thrombosis were more likely to have concentrations below the fifth percentile (N = 26, P < 0.05). The main risks associated with hemorrhages were abnormal concentrations, a high HAS-BLED score, the patient's age, and the creatinine blood level. For thrombosis, a concentration below the fifth percentile was the only risk factor that was significant in our cohort. While D and R under current recommendation have a better benefit-risk ratio than warfarin, their safe usage could be further optimized by some degree of therapeutic monitoring.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antithrombins; Blood Coagulation; Chromatography, High Pressure Liquid; Dabigatran; Drug Monitoring; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Safety; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Tandem Mass Spectrometry; Thrombosis; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Blood Coagulation Factors; Cerebral Hemorrhage, Traumatic; Cerebral Intraventricular Hemorrhage; Clopidogrel; Deamino Arginine Vasopressin; Female; Fractures, Bone; Hematoma; Hematoma, Subdural, Intracranial; Hemostatics; Humans; International Normalized Ratio; Intracranial Hemorrhage, Traumatic; Male; Middle Aged; Pelvic Bones; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Subarachnoid Hemorrhage, Traumatic; Thrombosis; Warfarin

While in recent trials the dual pathway inhibition with aspirin plus rivaroxaban has shown to be efficacious in patients with atherosclerotic cardiovascular disease, little is known about the effects of this combination treatment on thrombus formation and vascular remodelling upon vascular damage. The aim of this study was to examine the effects of aspirin and/or rivaroxaban on injury-induced murine arterial thrombus formation in vivo and in vitro, vessel-wall remodelling, and platelet-leukocyte aggregates. Temporary ligation of the carotid artery of C57BL/6 mice, fed a western type diet, led to endothelial denudation and sub-occlusive thrombus formation. At the site of ligation, the vessel wall stiffened and the intima-media thickened. Aspirin treatment antagonized vascular stiffening and rivaroxaban treatment led to a positive trend towards reduced stiffening. Local intima-media thickening was antagonized by both aspirin or rivaroxaban treatment. Platelet-leukocyte aggregates and the number of platelets per leukocyte were reduced in aspirin and/or rivaroxaban treatment groups. Furthermore, rivaroxaban restricted thrombus growth and height in vitro. In sum, this study shows vascular protective effects of aspirin and rivaroxaban, upon vascular injury of the mouse artery.

Topics: Animals; Arteries; Aspirin; Blood Platelets; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Factor Xa Inhibitors; Leukocytes; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis

Thrombosis is a pathological coagulation process and can lead to many serious thrombotic diseases. Here, we report a novel potent antithrombotic compound (6k) based on isosteviol with anticoagulant and antiplatelet activities. 6k selectively inhibited FXa (K

Topics: Animals; Diterpenes, Kaurane; Drug Discovery; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Partial Thromboplastin Time; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Thrombin; Thrombosis

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

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

Low-dose rivaroxaban was effective in secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the COMPASS trial. There is no established role, however, for oral anticoagulants in primary prevention. We evaluated whether coronary artery calcium (CAC) scoring identifies a high-risk primary prevention adult population who may benefit from low-dose rivaroxaban to prevent ASCVD events. We modeled expected outcomes of low-dose rivaroxaban in 5,196 Multiethnic Study of Atherosclerosis (MESA) cohort participants not already on antiplatelet or anticoagulant therapy. We applied relative risk ratios from COMPASS to absolute MESA event rates in order to estimate number needed to treat (NNT) to avoid a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, as well as number needed to harm (NNH) to cause 1 hospitalized bleed; with both NNT and NNH stratified by calculated ASCVD risk and by baseline CAC. MESA participants with CAC ≥300 had crude ASCVD event rate of 20 per 1000 patient-years, which is comparable to that observed in the COMPASS control-arm. CAC was independently associated with the composite ASCVD outcome (p <0.001 for trend). However, CAC was not independently associated with adjusted hazard ratio for hospitalized major bleeding. Predicted 5-year NNT (modeled from COMPASS) was 75 in persons with CAC 100-299 and 45 with CAC ≥300 despite NNH values of 252 and 98, respectively. In conclusion, CAC helps to distinguish estimated ASCVD benefit from estimated bleeding harm, thereby identifying very high-risk primary prevention adults without established cardiovascular disease who may derive net-benefit from low-dose rivaroxaban.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Calcium; Coronary Vessels; Dose-Response Relationship, Drug; Ethnicity; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Primary Prevention; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Survival Rate; Thrombosis; Tomography, X-Ray Computed; United States

We report a case of atrial fibrillation with rheumatic heart disease (RHD) who had intracardiac thrombus and cardiogenic cerebral embolism with rivaroxaban therapy. Intracardiac thrombus disappeared after switching from rivaroxaban to warfarin. Patients of RHD have the possibility of gradual progression of valvular disease even if they are old, so we need to distinguish nonvalvular atrial fibrillation from RHD before starting direct oral anticoagulants.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Brain Infarction; Drug Substitution; Factor Xa Inhibitors; Humans; Intracranial Embolism; Male; Rheumatic Heart Disease; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

Direct oral anticoagulants are not approved for use in patients with mechanical valves. When used to replace vitamin K antagonists, they may cause catastrophic consequences. The authors describe the case of a patient who, after discontinuation of warfarin and introduction of rivaroxaban, developed thrombosis of his mechanical mitral prosthesis.

Topics: Aged; Factor Xa Inhibitors; Heart Valve Prosthesis; Humans; Male; Mitral Valve; Rivaroxaban; Thrombosis; Treatment Failure

Both warfarin and nonvitamin K antagonist oral anticoagulants (NOACs) are increasingly used for thromboembolic prevention in patients with nonvalvular atrial fibrillation (NVAF). However, there are limited data concerning anticoagulation for left atrial (LA) thrombus or sludge. We aimed to determine the efficacy of warfarin and NOACs in LA thrombus or sludge in patients with NVAF or atrial flutter (AFL).. Seventy-two patients with LA thrombus or sludge were analyzed who were scheduled for catheter ablation of NVAF or AFL between December 2015 and November 2018. Baseline demographics, the nature and duration of anticoagulation therapy and LA thrombus or sludge resolution were recorded.. Compared with warfarin, dabigatran and rivaroxaban can also effectively resolve LA thrombus or sludge with no significant differences. Increasing the duration of anticoagulation, determining the optimal dosage of anticoagulants, and switching to another anticoagulant when necessary could be considered to improve treatment effectiveness.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Heart Atria; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vitamin K; Warfarin

Population ageing in developed countries will inevitably increase the need for knee and hip replacement surgery. Over the years, direct oral anticoagulants, such as rivaroxaban, have been widely used for thromboprophylaxis in patients undergoing knee and hip replacement surgery. The study of pharmacogenetic characteristics of rivaroxaban is important for enhancing the effectiveness and safety of rivaroxaban thromboprophylaxis.. Evaluation of CYP3A4, CYP3A5 and ABCB1 gene polymorphisms influence on rivaroxaban pharmacokinetics and prothrombin time dynamics in patients undergoing total hip and knee replacement surgery.. The study included 78 patients undergoing total hip and knee replacement surgery. The patients received 10 mg of rivaroxaban once a day. Genotyping of polymorphisms ABCB1 rs1045642, ABCB1 rs4148738, CYP3A4 rs35599367 and CYP3A5 rs776746 was performed. Peak steady-state and trough steady-state rivaroxaban concentrations were determined. Prothrombin time was also evaluated.. The study revealed the following haplotypes: (1) ABCB1 rs1045642-CYP3A4 rs35599367 and (2) ABCB1 rs4148738-CYP3A4 rs35599367. The analysis of the peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes revealed no significant differences. However, there was a statistically significant average correlation between peak steady-state rivaroxaban concentration and prothrombin time (r = 0.421; r. No significant difference was identified in peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes. The revealed statistically significant average correlation between the prothrombin time and peak steady-state rivaroxaban concentration is important in clinical practice for assessing the anticoagulant activity of rivaroxaban.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; ATP Binding Cassette Transporter, Subfamily B; Cytochrome P-450 CYP3A; Drug Monitoring; Factor Xa Inhibitors; Female; Haplotypes; Humans; Male; Middle Aged; Pharmacogenomic Variants; Prothrombin Time; Rivaroxaban; Thrombosis; Treatment Outcome

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Thrombosis; Vitamin K

Topics: Acute Disease; Anemia, Iron-Deficiency; Anticoagulants; Cardiotonic Agents; Case-Control Studies; Diuretics; Factor Xa Inhibitors; Heart Aneurysm; Heart Failure; Humans; Hypertension; Iron; Myocardial Infarction; Pacemaker, Artificial; Percutaneous Coronary Intervention; Placebos; Portraits as Topic; Rivaroxaban; Stroke; Stroke Volume; Thrombosis; Urea

Topics: Administration, Oral; Aged, 80 and over; Anticoagulants; Echocardiography; Heart Atria; Humans; Male; Rivaroxaban; Thrombosis

Topics: Aspirin; Atherosclerosis; Chronic Disease; Clinical Trials as Topic; Death; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vascular Diseases

In recent years, oral factor Xa inhibitors have become a research focus as anticoagulant drugs. Zifaxaban is the first oral FXa inhibitor to enter clinical trials in China. The aim of this study was to determine the inhibitory effect of zifaxaban on thrombosisthrough a model ofinferior vena cava (IVC) thrombosis in rabbits. IVC thrombosis model was established by electrical injury and stenosis, and zifaxaban was administered (p.o.) for 5 consecutive days, then coagulation indicators and bleeding were observed. The results showed that zifaxaban had obvious inhibitory effects on FXa, and had a significant inhibitory effect on IVC thrombosis induced by electrical damage and stenosis. The effect of zifaxaban was similar to that of rivaroxaban, but the bleeding side-effects of zifaxaban were less severe than those of rivaroxaban. Zifaxaban could prolong the prothrombin time and activated partial thromboplastin time of plasma similar to that of other oral FXa inhibitors. Zifaxaban had a significant inhibitory effect on FXa, but it had no obvious effect on other coagulation factors, major anticoagulant factors or fibrinolytic indices. Our results suggest that zifaxaban had specific inhibitory effects on FXa and inhibited IVC thrombosis in rabbits with its hemorrhagic effect was less than that of rivaroxaban. Zifaxaban is ecpected to be developed as a new drug for the prevention of deep venous thrombosis, providing more medication options for patients with such disease, more research is required to support it in the future.

Topics: Animals; Anticoagulants; China; Constriction, Pathologic; Factor Xa Inhibitors; Hemorrhage; Humans; Rabbits; Rivaroxaban; Thrombosis; Vena Cava, Inferior

Topics: Aged; Aged, 80 and over; Antidotes; Factor Xa; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Postoperative Hemorrhage; Practice Guidelines as Topic; Pyrazoles; Pyridones; Recombinant Proteins; Rivaroxaban; Thrombophilia; Thrombosis; Treatment Outcome

There is increasing evidence that bioprosthetic valve thrombosis (BPVT) is more common than previously thought. However, there are very few cases describing the occurrence of BPVT on therapeutic anticoagulation, and no previous cases are available stating the occurrence of BPVT on direct oral anticoagulant therapy. We describe the case of surgically managed aortic BPVT that was diagnosed while the patient was on rivaroxaban.

Topics: Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Bioprosthesis; Echocardiography, Transesophageal; Factor Xa Inhibitors; Female; Heart Diseases; Heart Valve Prosthesis; Heart Ventricles; Humans; Prosthesis Failure; Rivaroxaban; Thrombosis

We report the case of a morbidly obese 49-year-old female found to have a 16×14×10 cm high grade myxoid liposarcoma of the thigh initially diagnosed as a hematoma. Recent initiation of rivaroxaban for a coincident ipsilateral popliteal vein thrombosis placed hematoma high in the differential diagnosis. Despite its large size, the mass was not directly appreciable on physical exam due to excess adjacent adipose tissue. Diagnostic success was achieved only after anchoring bias was abandoned and adaptive expertise was applied.

Topics: Diagnosis, Differential; Diagnostic Errors; Factor Xa Inhibitors; Female; Hematoma; Humans; Liposarcoma, Myxoid; Middle Aged; Obesity, Morbid; Popliteal Vein; Rivaroxaban; Thigh; Thrombosis

Thrombosis remains a major cause of morbidity and mortality. Consequently, advances in antithrombotic therapy are needed to reduce the disease burden. This article focuses on 2 such advances. First, the prevention of atherothrombosis in patients with coronary or peripheral artery disease, which has been enhanced by the finding that the combination of low-dose rivaroxaban plus aspirin is superior to aspirin alone for prevention of recurrent ischemic events. However, this benefit comes at the cost of increased bleeding albeit not fatal bleeding. To overcome this problem, the second advance is the identification of factor XI as a target for new anticoagulants that are potentially safer than those currently available.

Topics: Aspirin; Clinical Trials as Topic; Factor XI; Factor XII; Fibrinolytic Agents; Humans; Rivaroxaban; Thrombosis

Topics: Adult; Aged; Diagnosis, Differential; Echocardiography; Factor Xa Inhibitors; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Rivaroxaban; Thrombosis

It is not known whether direct-acting oral anticoagulants (DOACs), such as dabigatran, apixaban, and rivaroxaban increase the risk of bleeding complications during or after coronary catheterization. The aim of this study was to investigate the safety of uninterrupted DOAC treatment during diagnostic radial coronary angiography (CAG).. This study included 160 patients who underwent diagnostic radial cardiac catheterization. The 60 patients in the group who were using a DOAC (apixaban, rivaroxaban, or dabigatran) were enrolled in a Group A. Post-procedure results from patients in Group A were compared with those of an age- and sex-matched control group (Group B) that included 100 patients who underwent radial CAG who did not use a DOAC.. There was no significant difference in the procedure and compression times, creatinine level, or presence of hypertension, diabetes mellitus, smoking, alcohol use, vascular disease, or congestive heart failure between the 2 groups. During the 1 -month follow-up period, only 1 radial occlusion was registered in the control group (Group B). There was no case of a large hematoma (>5 cm or extending to the forearm), dissection, fistula, perforation, or compartment syndrome. Hematomas smaller than 5 cm were seen in 2 patients (1 in each group). No thrombotic events were observed during follow-up examinations.. Performing radial CAG with uninterrupted DOAC treatment appears to carry no risk of increased early or short-term complications. The simple, uninterrupted DOAC strategy is comfortable, easy, and safe.

Topics: Aged; Anticoagulants; Cardiac Catheterization; Coronary Angiography; Dabigatran; Female; Hematoma; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis

Topics: Anticholesteremic Agents; Aspirin; Cholesterol, LDL; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; PCSK9 Inhibitors; Plaque, Atherosclerotic; Rivaroxaban; Thrombosis

A 63-year-old woman with known antiphospholipid syndrome (APLS) presented with catastrophic APLS and multiorgan dysfunction after a change in her anticoagulation from warfarin to rivaroxaban. Evidence suggests direct-acting oral anticoagulants (DOACs) like rivaroxaban may be less effective than warfarin in secondary prevention of thrombotic events in high-risk APLS patients.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Middle Aged; Rivaroxaban; Secondary Prevention; Thrombosis; Warfarin

Topics: Fibrinolytic Agents; Heart Failure; Humans; Rivaroxaban; Thromboembolism; Thrombosis

Direct acting oral anticoagulants (DOACs) are increasingly used as off-label alternatives to vitamin K antagonists for the treatment of left ventricular (LV) thrombus. However, efficacy data is limited to small case series and one meta-analysis of case reports. We aimed to determine the efficacy and safety of DOACs in treatment of LV thrombus utilizing transthoracic echocardiography (TTE) and clinical outcomes. We identified 52 patients (mean age = 64 years, 71% men) treated with a DOAC for LV thrombus (n = 26 apixaban, n = 24 rivaroxaban, and n = 2 dabigatran). Thirty-five of the 52 patients had a follow-up TTE after DOAC initiation. The primary end point was defined as resolution of LV thrombus (in patients with a subsequent TTE), or death, major bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke, or peripheral embolization. An experienced echocardiographer (M.L.M.) reviewed all TTEs for presence or absence of LV thrombus without knowledge of time point or clinical data. Twenty-nine of the 35 (83%) patients who underwent follow-up TTE had resolution of LV thrombus, with a mean duration of 264 days. Of the total study population, there was 1 cardioembolic event (transient ischemic attack) 52 days after initiating DOAC, 3 gastrointestinal bleeds requiring transfusion, and 1 patient with epistaxis requiring transfusion. All patients with a hemorrhagic complication were receiving concomitant antiplatelet therapy. DOAC therapy appears promising for the treatment of LV thrombus. A larger, prospective study is warranted to confirm these results.

Topics: Adult; Aged; Blood Transfusion; Dabigatran; Echocardiography; Epistaxis; Factor Xa Inhibitors; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Heart Ventricles; Humans; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thrombosis; Ventricular Dysfunction, Left

Topics: Aspirin; Factor Xa Inhibitors; Hospitalization; Humans; Placebo Effect; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis; Venous Thromboembolism

Topics: Cohort Studies; Humans; Permeability; Rivaroxaban; Thrombosis; Venous Thromboembolism

Cancer is a known hypercoagulable state that leads to an increased risk of venous thromboembolism (VTE). Low molecular weight heparin remains the preferred anticoagulant for VTE in patients with cancer over vitamin K antagonist. However, the preferred anticoagulant in prevention of stroke and systemic embolism in atrial fibrillation (AF) in patients with cancer has yet to be determined. The direct oral anticoagulants (DOACs) are increasingly being utilized; however their role in cancer has only recently been investigated. The objective of this retrospective cohort was to describe real-world anticoagulation prescribing patterns in cancer patients at a large academic medical center between January 1, 2013 and October 31, 2016. We sought to assess the safety, tolerability, and efficacy of DOACs in patients with cancer for either VTE and/or AF. Patient demographic, clinical characteristics, as well as bleeding and thrombotic events were collected. There were 214 patients in our analysis, of which 71 patients (33%) received a DOAC [apixaban (n = 22), dabigatran (n = 17), and rivaroxaban (n = 32)]. There were fewer bleeding events and/or discontinuations in the DOAC group compared to enoxaparin (13 vs. 27, p = 0.022). There was no difference in major or minor bleeds or thromboembolic events in comparing DOAC to enoxaparin or DOAC to warfarin. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs compared to warfarin or enoxaparin in patients with cancer. DOACs may represent an alternative to warfarin or enoxaparin in patients with cancer for VTE and/or stroke reduction in AF.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Enoxaparin; Hemorrhage; Humans; Middle Aged; Neoplasms; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thrombosis; Treatment Outcome; Venous Thromboembolism; Warfarin

The aims of the present study were to describe the proportion of patients eligible for the COMPASS trial within the Reduction of Atherothrombosis for Continued Health (REACH) registry, the reasons for ineligibility, and to put in perspective the characteristics and outcomes of trial-eligible patients from the REACH registry compared with those of patients enrolled in the reference aspirin arm of the COMPASS trial.. The COMPASS selection and exclusion criteria were applied to REACH patients with either coronary artery disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or stroke. In REACH, 31 873 patients had CAD or PAD and detailed information allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the inclusion criteria and thus were not eligible. The 'COMPASS-Eligible' population therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI with stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%). COMPASS-Eligible patients from REACH experienced higher annualized primary outcome event rates than patients actually enrolled in the reference aspirin arm of COMPASS (4.2% vs. 2.9% per year, P < 0.001).. COMPASS-Eligible patients represent a substantial fraction of stable CAD/PAD patients encountered in routine clinical practice in the large international REACH registry suggesting good external applicability. COMPASS-Eligible patients experienced a higher rate of the primary outcome compared with COMPASS participants in the aspirin alone treatment arm.

Topics: Aged; Aspirin; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Patient Selection; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Registries; Rivaroxaban; Thrombosis

Topics: Aspirin; Blood Coagulation; Cardiovascular Diseases; Clinical Decision-Making; Evidence-Based Medicine; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disorder related to thrombosis. Anticoagulant therapy is suggested for the treatment of this disease. The success of the novel oral anticoagulant rivaroxaban as a treatment option for this disorder is unclear.. A 43-year-old man who felt dizzy at rest was found to have an intraventricular thrombus.. The thrombus was confirmed by echocardiography. And LVNC was diagnosed by cardiac magnetic resonance (CMR) and echocardiography.. He was prescribed a low dose (10 mg daily) of rivaroxaban as treatment.. After 3 months, the thrombus diminished, and the manifestation disappeared.. Low dose of rivaroxaban may serve as a viable option for anticoagulation therapy in LVNC patients, with large clinical trials needed to determine the best course of treatment.

Topics: Adult; Factor Xa Inhibitors; Humans; Isolated Noncompaction of the Ventricular Myocardium; Male; Rivaroxaban; Thrombosis; Ventricular Dysfunction, Left

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Thrombosis

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Thrombosis

Case report of a patient with age-related macular degeneration whose digital ischemia can most plausibly be attributed to ranibizumab.. To report ranibizumab as the probable cause of digital ischemia in a patient treated for age-related macular degeneration.. Single-patient case report.. An 83-year-old woman with an unremarkable medical history suffered acute ischemia in her left hand with necrosis of the distal phalange of the fifth finger after six intravitreal injections of ranibizumab. Her etiological work-up was negative. Her condition improved after endovascular revascularization and remained good at six months' follow-up after three months of dual antithrombotic therapy (low molecular weight heparin then rivaroxaban, both with aspirin) followed by rivaroxaban alone and four courses of intravenous iloprost.. The increased incidence of peripheral arterial thromboembolic events in patients under ranibizumab treatment is slight but significant, with 0.8-5% of patients affected, most of which suffer strokes. These events seem to occur at a random time after ranibizumab treatment is initiated and no reliable marker has yet been identified. The most probable cause of digital ischemia in our patient was ranibizumab.

Topics: Aged, 80 and over; Angiogenesis Inhibitors; Angioplasty; Aspirin; Combined Modality Therapy; Female; Fingers; Heparin, Low-Molecular-Weight; Humans; Iloprost; Intravitreal Injections; Ischemia; Macular Degeneration; Radial Artery; Ranibizumab; Rivaroxaban; Thrombectomy; Thrombosis; Ulnar Artery; Vascular Endothelial Growth Factor A

Topics: Adult; Blood Coagulation; Echocardiography; Factor Xa Inhibitors; Heart Diseases; Heart Ventricles; Humans; Male; Rivaroxaban; Thrombosis

Topics: Antibodies, Antiphospholipid; Anticoagulants; Humans; Recurrence; Rivaroxaban; Thrombosis; Treatment Outcome; Vitamin K

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Coagulation; Blood Platelets; Factor Xa Inhibitors; Female; Flow Cytometry; Humans; Inflammation Mediators; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Platelet Activation; Platelet Aggregation; Rivaroxaban; Thrombin; Thrombosis

Left atrial thrombus (LAT) and dense spontaneous echocardiographic contrast (SEC) detected by transesophageal echocardiography (TEE) in patients on continuous direct oral anticoagulants (DOAC) therapy before catheter ablation of atrial fibrillation (AF) or atrial flutter (AFL) have been described.. We sought to compare rates of TEE-detected LAT and dense SEC among patients taking different DOACs.. We evaluated 609 consecutive patients from 3 tertiary hospitals (median age 65 years; interquartile range 58-71 years; 436 (72%) men) who were on ≥4 weeks of continuous DOAC therapy (dabigatran, n = 166 [27%]; rivaroxaban, n = 257 [42%]; or apixaban, n = 186 [31%]) undergoing TEE before catheter ablation of AF/AFL. Demographic, clinical, and TEE data were collected for each patient.. Despite ≥4 weeks of continuous DOAC therapy, 17 patients (2.8%) had LAT and 15 patients (2.5%) had dense SEC detected by TEE. The rates of LAT were 3.0%, 3.5%, and 1.6% for patients on dabigatran, rivaroxaban, and apixaban, respectively (P = .482). The rates of dense SEC were 1.2%, 3.5%, and 2.2% for patients on dabigatran, rivaroxaban, and apixaban, respectively (P = .299). Congestive heart failure (odds ratio 4.4; 95% confidence interval 1.6-12; P = .003) and moderate/severe left atrial enlargement (odds ratio 3.1; 95% confidence interval 1.1-8.6; P = .026) were independent predictors of LAT.. In this study, ∼3% of patients on continuous DOAC therapy had LAT detected before catheter ablation of AF/AFL. Specific DOAC therapy did not significantly affect the rates of LAT detection.

Topics: Administration, Oral; Aged; Antithrombins; Atrial Fibrillation; Catheter Ablation; Contrast Media; Dabigatran; Dose-Response Relationship, Drug; Echocardiography, Transesophageal; Factor Xa Inhibitors; Female; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thrombosis

Guidelines recommend the use of multiple pharmacologic agents and/or mechanical compressive devices for prevention of venous thromboembolism, but preference for any specific agent is no longer given in regard to safety or efficacy.. To compare postoperative bleeding rates in patients receiving enoxaparin, rivaroxaban, or aspirin for thromboprophylaxis after undergoing elective total hip arthroplasty or total knee arthroplasty.. This retrospective cohort analysis evaluated patients who received thromboprophylaxis with either enoxaparin, rivaroxaban, or aspirin. All data were collected from the electronic medical record. The primary outcome was any postoperative bleeding.. A total of 1244 patients were included with 366 in the aspirin, 438 in the enoxaparin, and 440 in the rivaroxaban arms. Those who received aspirin or enoxaparin were less likely to experience any bleeding compared to those patients who received rivaroxaban ( P < .05). There was also a lower rate of major bleeding in these groups, but the differences were not significant.. Aspirin and enoxaparin conferred similar bleeding risks, and both exhibited less bleeding than patients who received rivaroxaban.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Blood Loss, Surgical; Enoxaparin; Female; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Thrombosis

Left ventricular thrombi are mostly seen in the akinetic segments of left ventricle and warfarin is the golden standard treatment. In our case, a 67-year-old male patient with ischemic dilated cardiomyopathy and atrial fibrillation was under warfarin treatment, but due to fluctuations in international normalized ratio, warfarin was discontinued and changed to rivaroxaban (20 mg once a day). He had a fixed thrombus measuring 1.80 × 1.12 cm

Topics: Aged; Atrial Fibrillation; Blood Coagulation; Drug Monitoring; Drug Substitution; Echocardiography; Factor Xa Inhibitors; Humans; International Normalized Ratio; Male; Prothrombin Time; Rivaroxaban; Thromboembolism; Thrombosis; Treatment Outcome; Warfarin

In recent years, the concept of treatment after surgery in the department of orthopedics has changed from hemostasis to anticoagulant. This article analyses the safety and effectiveness of anticoagulants for prophylactic anticoagulants after spinal fractures. By analyzing the incidence of bleeding and VTE in 2 weeks after operation, there was no significant difference between the 2 groups (P>0.05), but the incidence of VTE in rivaroxaban group was significantly lower than that in control group. In conclusion, the rivaroxaban oral anticoagulants are stable, safe and easy to use. It significantly reduced the incidence of VTE after spinal fracture and nerve injury, and did not increase the risk of bleeding. It is an ideal type of prophylactic anticoagulant after the operation of spinal fracture, which is worthy of further clinical study.

Topics: Fracture Fixation, Internal; Humans; Postoperative Complications; Retrospective Studies; Rivaroxaban; Spinal Fractures; Thrombosis

Left ventricular (LV) thrombus is a major complication of acute systolic cardiomyopathy especially after a large anterior myocardial infarction (AMI), and it poses a significant embolic risk, up to five times higher than the general population. Current guidelines for LV thrombi recommend vitamin K antagonist for anticoagulation in contrast to novel oral anticoagulants (NOACs) which have not been studied well in cases of LV thrombus. We present a case of patient with AMI, who was noted to have severe systolic dysfunction and a large LV thrombus which was successfully treated with rivaroxaban therapy with complete resolution of LV thrombus on two months follow-up.

Topics: Administration, Oral; Anticoagulants; Heart Diseases; Humans; Myocardial Infarction; Rivaroxaban; Thrombosis; Time Factors

Blood loss and deep vein thrombosis (DVT) are important complications after total knee arthroplasty (TKA). Topical tranexamic acid (TXA) effectively reduces wound bleeding but may elevate the risk of DVT. In contrast, rivaroxaban potently prevents DVT but has been associated with bleeding complications. The simultaneous use of topical TXA and rivaroxaban in TKA has not been much investigated.. A retrospective cohort study was conducted with two consecutive groups of patients who underwent TKA. Intraoperatively, one group (RVTX group) received topical, intraarticular TXA, while the other (RV group) did not. Both groups were administered rivaroxaban postoperatively for 14 days and underwent Doppler ultrasound for DVT screening. After propensity score matching, both groups consisted of 52 patients (104 patients in total) and were compared regarding total drain output, nadir haemoglobin (Hb), maximum Hb decrease, calculated total blood loss, transfusion rate, and incidence of DVT and wound complications.. Both groups showed no significant differences in the propensity-matched variables of age, sex, body mass index, American Society of Anesthesiologists physical status score, and preoperative Hb. The RVTX group showed a significantly higher nadir Hb (p < 0.001), lower drain output (p < 0.001), Hb decrease (p = 0.015), total blood loss (p < 0.001), and rate of transfusion (p < 0.001) and fewer wound complications (p = 0.027). However, the incidence of DVT (p = 1.000) did not differ significantly between the two groups, and all cases were asymptomatic.. The combined use of intraarticular topical TXA with rivaroxaban in patients undergoing TKA is a safe and effective method to reduce blood loss, the need for transfusion, and wound complications without elevating the risk of DVT.

Topics: Administration, Topical; Aged; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Retrospective Studies; Risk Factors; Rivaroxaban; Surgical Wound Infection; Thrombosis; Tranexamic Acid

Topics: Aspirin; Atherosclerosis; Atrial Fibrillation; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Receptors, Purinergic P2Y12; Rivaroxaban; Thrombosis

Topics: Humans; Rivaroxaban; Stroke; Thrombosis

Essentials Activated clotting factor X (FXa) acquires fibrinolytic cofactor function after cleavage by plasmin. FXa-mediated plasma fibrinolysis is enabled by active site modification blocking a second cleavage. FXa-directed oral anticoagulants (DOACs) alter FXa cleavage by plasmin. DOACs enhance FX-dependent fibrinolysis and plasmin generation by tissue plasminogen activator.. When bound to an anionic phospholipid-containing membrane, activated clotting factor X (FXa) is sequentially cleaved by plasmin from the intact form, FXaα, to FXaβ and then to Xa33/13. Tissue-type plasminogen activator (t-PA) produces plasmin and is the initiator of fibrinolysis. Both FXaβ and Xa33/13 enhance t-PA-mediated plasminogen activation. Although stable in experiments using purified proteins, Xa33/13 rapidly loses t-PA cofactor function in plasma. Bypassing this inhibition, covalent modification of the FXaα active site prevents Xa33/13 formation by plasmin, and the persistent FXaβ enhances plasma fibrinolysis. As the direct oral anticoagulants (DOACs) rivaroxaban and apixaban bind to the FXa active site, we hypothesized that they similarly modulate FXa fibrinolytic function.. DOAC effects on fibrinolysis and the t-PA cofactor function of FXa were studied in patient plasma, normal pooled plasma and purified protein experiments by the use of light scattering, chromogenic assays, and immunoblots.. The plasma of patients taking rivaroxaban showed enhanced fibrinolysis correlating with FXaβ. In normal pooled plasma, the addition of rivaroxaban or apixaban also shortened fibrinolysis times. This was related to the cleavage product, FXaβ, which increased plasmin production by t-PA. It was confirmed that these results were not caused by DOACs affecting activated FXIII-mediated fibrin crosslinking, clot ultrastructure and thrombin-activatable fibrinolysis inhibitor activation in plasma.. The current study suggests a previously unknown effect of DOACs on FXa in addition to their well-documented anticoagulant role. By enabling the t-PA cofactor function of FXaβ in plasma, DOACs also enhance fibrinolysis. This effect may broaden their therapeutic indications.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Catalytic Domain; Cross-Linking Reagents; Factor Xa; Factor Xa Inhibitors; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Phospholipids; Pyrazoles; Pyridones; Rivaroxaban; Thrombin; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator

Topics: Acute Coronary Syndrome; Aspirin; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome

Topics: Anticoagulants; Drug Resistance; Echocardiography; Heart Ventricles; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Warfarin

Anti-thrombosis therapy for atrial fibrillation (AF) management and stroke prevention is an important aspect of disease management. Novel oral anticoagulants (NOACs) are recommended by guidelines for AF management. However, if one can switch one NOAC to another when the former showed a poor effect has not been fully determined.. A 52-year-old man was admitted to our center for heart failure and AF with a thrombus in the left atrium.. Cardiomyopathy was diagnosed by cardiac magnetic resonance (CMR) and echocardiography.. He was prescribed rivaroxaban (20 mg daily) as treatment, and dabigatran (150 mg twice daily) was used when the thrombus was found to be non-response to rivaroxaban.. The rivaroxaban did not diminish the atrial thrombus, and dabigatran was given instead which finally eliminated the thrombus.. Individualized responsiveness to NOACs should be considered and paid more attention to during clinical practice.

Topics: Antithrombins; Atrial Fibrillation; Dabigatran; Drug Resistance; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis

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

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

Atrial fibrillation is the most common cardiac arrhythmia. It is responsible for up to 20% of all ischemic strokes. Rate control and anticoagulation are crucial for atrial fibrillation management and stroke prevention.. We present the case of an 84-year-old Italian woman with a left atrial appendage thrombus that developed despite her use of anticoagulant therapy with warfarin for a previous pulmonary embolism. She had atrial fibrillation and heterozygosity for both factor V Leiden and methylenetetrahydrofolate reductase C677T mutation, thus creating resistance to activated protein C. Anticoagulant therapy was switched to heparin for 1 week and then to rivaroxaban. After 3 months of rivaroxaban use, the thrombus disappeared.. This case raises the issue of the ineffectiveness of warfarin therapy in complex cases involving particular thrombophilic conditions and the possibility of using rivaroxaban as a safe and effective alternative.

Topics: Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Female; Humans; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is a promising target for anticoagulation drugs. Three oral FXa inhibitors have been approved by FDA for treating thrombotic diseases. In this study, 43 novel compounds were synthesized anthranilamide-based FXa inhibitors aiming to ameliorate the toxicity of traditional FXa inhibitors in clinic. The data indicated that the compounds 6a, 6a-b, 6a-e, 6k, 6k-a and 6k-b showed remarkable FXa inhibitory activity and excellent selectivity over thrombin in vitro. Selected compounds also exhibited anticoagulant activities in vitro consequently and were potent novel anti-coagulators in further.

Topics: Adult; Anticoagulants; Blood Coagulation; Computational Biology; Factor Xa; Factor Xa Inhibitors; Humans; Male; Models, Molecular; Molecular Targeted Therapy; ortho-Aminobenzoates; Plasma; Rivaroxaban; Thrombin; Thrombosis

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Treatment Failure; Young Adult

BACKGROUND Although transcatheter aortic valve replacement (TAVR) has become a worldwide and generally accepted treatment of patients with aortic stenosis at high surgical risk, there is a rising concern and debate about the occurrence of transcatheter heart valve (THV) thrombosis and its impact on TAVR outcome. It seems that the incidence of THV thrombosis is higher than first anticipated, but uncertainty remains regarding how to prevent and how to treat it. Hence, there is an urgent need for understanding THV thrombosis and to communicate experiences within the field. CASE REPORT We present a unique case of late occurrence of THV thrombosis that was resolved by switching from clopidogrel to rivaroxaban treatment. CONCLUSIONS As a novel observation, our case demonstrates that THV thrombosis may develop even late after TAVR, and even in such cases may be completely reversed. It also underscores that THV dysfunction should evoke prompt investigation for possible thrombus formation, preferable by multidetector computed tomography. Finally, this case report suggests NOAC as an alternative to warfarin treatment in patients with THV thrombosis.

Topics: Aged; Aortic Valve Stenosis; Factor Xa Inhibitors; Heart Valve Prosthesis; Humans; Male; Rivaroxaban; Thrombosis; Transcatheter Aortic Valve Replacement

Endovenous heat-induced thrombosis (EHIT) is a well-described complication of endovenous laser ablation (EVLA). We report our centers' experience on the efficacy (EHIT level ≥2 according to the Kabnick classification) and safety (observed major and minor bleeding events) of rivaroxaban for EHIT prophylaxis in EVLA with and without concomitant phlebectomy.. Demographic, procedural, and outcome data of all patients with EVLA of the great, accessory, or small saphenous vein and EHIT prophylaxis with 10 mg/d rivaroxaban between 2012 and 2014 were reviewed and analyzed in this investigator-initiated multicenter retrospective observational single-arm study.. During a median (interquartile range) follow-up duration of 51 (41-68) days, complete vein occlusion was achieved in 98.4% of 438 EVLA procedures in 306 patients. One patient had an EHIT level 2 (0.2%; 95% confidence interval, 0.006%-1.3%). No major bleedings (0%; 95% confidence interval, 0.0%-0.8%) and six minor bleedings (1.4%; 95% confidence interval, 0.5%-3%) were observed.. Rivaroxaban (10 mg/d) for 5 to 10 days seems to be an efficacious and safe alternative for EHIT prophylaxis in EVLA with or without phlebectomy.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Laser Therapy; Male; Middle Aged; Popliteal Vein; Postoperative Complications; Retrospective Studies; Risk Factors; Rivaroxaban; Saphenous Vein; Switzerland; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Varicose Veins; Vascular Surgical Procedures; Venous Insufficiency

Patients with atrial fibrillation (AF) routinely undergo different imaging modalities for the evaluation of the left atrial (LA) appendage to rule out thrombus prior to the AF ablation procedure. Recently, uninterrupted novel oral anticoagulants were introduced for patients undergoing atrial fibrillation (AF) ablation to minimize the peri-procedural thromboembolism risk. We performed a retrospective analysis to evaluate the safety of uninterrupted rivaroxaban and whether transesophageal (TEE) or intracardiac echocardiography (ICE) is necessary for patients undergoing AF ablation.. Data from 332 consecutive patients (42% females, aged 64 ± 11 years) with AF undergoing either TEE (n = 115) prior to catheter ablation or ICE (n = 217) for the detection of LA thrombus were analyzed. All patients were on uninterrupted rivaroxaban during, and for at least, 4 weeks before the procedure. Heparin bolus was administered in all patients before transseptal puncture to maintain a target activated clotting time of >350 s.. A total of 277 patients (80.4%) had paroxysmal AF. The average CHA2DS2-VASc score was 2.11 ± 0.91 in the TEE group and 2.46 ± 0.61 in the ICE group. The CHA2DS2-VASc score was ≥2 in 64 (55.7%) and 214 (98.6%) patients in the TEE and ICE groups, respectively. The left atrial appendage was adequately visualized in all cases. None of the patients have an identifiable LA thrombus either in the TEE group or the ICE group. One (0.3%) thromboembolic periprocedural stroke occurred in a patient with long-standing persistent AF in the TEE group.. This study illustrates that performing AF ablation with ICE guidance on uninterrupted rivaroxaban for at least 4 weeks even without TEE is feasible and safe.

Topics: Administration, Oral; Aged; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Drug Administration Schedule; Echocardiography, Transesophageal; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Risk Factors; Rivaroxaban; Thrombosis; Time Factors; Treatment Outcome

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

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

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

Patients with persistent atrial fibrillation (AF) and a large left atrium are at a high risk for thromboembolisms. Recently, direct oral anticoagulants (DOACs) have mainly been used for the prevention of cardiac embolisms caused by AF. Transesophageal echocardiography (TEE) is performed in order to exclude any left atrial appendage (LAA) thrombi. We herein report two cases of persistent AF, both of which were treated with rivaroxaban for more than two years. Since TEE identified mobile LAA thrombi with this treatment, we switched from rivaroxaban to the direct thrombin inhibitor dabigatran. Dabigatran resolved the LAA thrombi that had been refractory to rivaroxaban.

Topics: Aged; Antithrombins; Atrial Appendage; Atrial Fibrillation; Dabigatran; Echocardiography, Transesophageal; Heart Atria; Humans; Male; Rivaroxaban; Thrombosis

Direct oral anticoagulants (DOACs) have low risk of intracranial hemorrhage compared to warfarin. We sought to clarify the different mechanisms responsible for suppression of bleeding events using the Total Thrombus-formation Analysis System (T-TAS), a flow-microchip chamber with thrombogenic surfaces. Blood samples were obtained at Off- and On-anticoagulant (trough) from 120 consecutive patients with atrial fibrillation (warfarin; n = 29, dabigatran; n = 19, rivaroxaban; n = 47, apixaban; n = 25), which were used for T-TAS to compute the area under the curve (AUC) (AR

Topics: Administration, Oral; Aged; Anticoagulants; Area Under Curve; Atrial Fibrillation; Dabigatran; Female; Humans; Lab-On-A-Chip Devices; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Warfarin

Antithrombotic medications target coagulation factors. Their use is associated with an increased bleeding risk. Safer drugs are needed. The heat shock protein 70 (Hsp70) exhibits antithrombotic properties that do not influence bleeding. By using murine models, we aimed to test the hypothesis that overexpressing Hsp70 with CM-695, a first in class dual inhibitor of HDAC6 and phosphodiesterase 9, protects against thrombosis while leaves bleeding tendency unaltered. CM-695 was used to induce Hsp70 overexpression. Hsp70 overexpressing mice were submitted to three thrombosis-triggering procedures. The ferric chloride carotid artery model was used to compare the antithrombotic role of CM-695 and rivaroxaban, a direct oral anticoagulant. The mouse tail transection model was used to compare the bleeding tendency upon CM-695 or rivaroxaban administration. Intraperitoneal (i. p.) 20 mg/kg CM-695 increased Hsp70 expression markedly in the murine aortic tissue. This treatment delayed thrombosis in the collagen/epinephrine [p=0.04 (Log-Rank test), n=10], Rose Bengal/laser [median vessel occlusion time (OT): 58.6 vs 39.0 minutes (min) in the control group (CG), p=0.008, n≥10] and ferric chloride (OT: 14.7 vs 9.2 min in the CG, p=0.032, n≥10) models. I.p. 80 mg/kg CM-695 (n≥9) and intravenous 3 mg/kg rivaroxaban (n≥8) significantly delayed thrombosis. CM-695 did not induce bleeding [median bleeding time (BT): 8.5 vs 7.5 min in the CG, n≥10]. However, BT was dramatically increased by rivaroxaban (30.0 vs 13.7 min in the CG, p=0.001, n=10). In conclusion, CM-695 is a new antithrombotic small molecule devoid of bleeding risk that may be envisioned as a useful clinical tool.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Bleeding Time; Blood Coagulation; Female; Fibrinolytic Agents; Hemorrhage; Histone Deacetylase 6; Histone Deacetylase Inhibitors; HSP70 Heat-Shock Proteins; Mice; Mice, Knockout; Nervous System Autoimmune Disease, Experimental; Phosphodiesterase Inhibitors; Risk Assessment; Rivaroxaban; Thromboembolism; Thrombosis; Time Factors; Up-Regulation

Topics: Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

The goal of anticoagulation management programs is to prevent thrombosis while minimizing the risks of hemorrhage. Direct acting oral anticoagulants (DOACs) selectively inhibit coagulation proteins to inhibit thrombosis. Previous studies suggest patient monitoring and education provided through anticoagulation services enhance adherence and decrease adverse outcomes in patients receiving DOAC therapy.. The objectives of this study were to describe DOAC prescribing adherence to anticoagulation service protocols and to observe whether enrollment in an anticoagulation service resulted in greater prescribing adherence to DOAC protocols.. A retrospective cohort study evaluated all initial prescriptions of apixaban, dabigatran, and rivaroxaban at Marshfield Clinic from 19 October 2010 to 21 August 2014. Three algorithms analyzed patient and prescription data extracted from the organization's electronic health record and classified prescriptions as per protocol or not per protocol. The algorithms classified not per protocol prescriptions as off-label indication, renal impairment [estimated glomerular filtration rate (eGFR) <30 ml/min], hepatic impairment (rivaroxaban and apixaban), advanced age >74 years (dabigatran), dose too low, or dose too high. The analysis assessed whether enrollment in the Marshfield Clinic Anticoagulation Service DOAC monitoring process was associated with increased adherence to protocols.. In aggregate, 72% of apixaban prescriptions, 52% of dabigatran prescriptions, and 70% of rivaroxaban prescriptions were per protocol. Off-label indications and dosage too low were the most common not per protocol reasons for apixaban and rivaroxaban prescriptions. Age ≥75 years and off-label indication were the most common not per protocol reasons for dabigatran prescriptions. Enrollment in the anticoagulation service process was not associated with increased adherence to protocols.. A significant proportion of DOAC prescriptions did not adhere to protocol expectations. While enrollment in DOAC management through the Marshfield Clinic Anticoagulation Service was not associated with increased adherence to protocols, opportunities exist to optimize DOAC prescribing. Defining ideal DOAC management requires additional research.

Topics: Administration, Oral; Adult; Age Factors; Aged; Algorithms; Anticoagulants; Cohort Studies; Dabigatran; Female; Guideline Adherence; Hemorrhage; Humans; Male; Middle Aged; Off-Label Use; Practice Guidelines as Topic; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thrombosis

Left ventricular thrombus (LVT) formation usually necessitates short term anticoagulation for thrombus resolution and to prevent embolic events. Historically, vitamin K antagonist therapy has been the treatment of choice. However, with the advent of direct acting anticoagulants, their role in the management of LVT is not clear. Patients were included if they had received rivaroxaban or apixaban for more than 1 day for LVT documented on imaging. The primary objective was resolution of LVT at 3 months based on assessment by an independent cardiologist review of initial and subsequent imaging results. The principle safety objective was to assess major or clinically relevant non-major bleeding using GUSTO, TIMI, and BARC bleeding criteria. During the 2-year study period seven patients were treated with rivaroxaban and three with apixaban. Two patients who had received apixaban and one on rivaroxaban were lost to follow up. In those with an initial and follow-up ECHO (n = 6) the median time to follow up imaging was 214 (IQR 33-414) days and complete LVT resolution was observed in 83% of patients. One patient on rivaroxaban had a bleeding events that was minimal (TIMI), Type 2 (BARC), or classified as mild (GUSTO) due to pulmonary hemorrhage. In those deemed not to be a candidate for vitamin K antagonist the use of rivaroxaban or apixaban may be a considered in the treatment of LVT. Further research in this area is needed to assess the efficacy and safety of using FXAI for treatment of LVT.

Topics: Adult; Aged; Diagnostic Imaging; Factor Xa Inhibitors; Female; Follow-Up Studies; Heart Ventricles; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Treatment Outcome

Direct oral anticoagulants have been shown safe and effective in the treatment of pulmonary emboli and deep vein thrombi. Their role in the treatment of patients with hypercoagulability is uncertain. We designed a retrospective exploratory analysis of all patients with definite heparin induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS) that were treated with either apixaban or rivaroxaban from September 2011 through November 2015. Patients were reviewed for several clinico-pathologic features, including efficacy and safety. 23 patients were identified (12 patients with HIT and 11 patients with APS). Sixteen patients (70 %) were treated with apixaban and seven patients (30 %) were treated with rivaroxaban over a median follow up of 7 months (range 2-39). Zero patients developed recurrent thrombi. Two patients being treated for HIT developed major bleeding leading to discontinuation of all anticoagulation. Therefore, apixaban and rivaroxaban appear safe and effective for treatment of patients with HIT and APS in this small retrospective cohort and should be considered on an individual basis for patients who refuse, fail or are intolerant of warfarin. There were no sources of funding.

Topics: Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Thrombophilia; Thrombosis

Topics: Administration, Oral; Aged; Anticoagulants; Endocarditis, Non-Infective; Female; Heparin; Humans; Pancreatic Neoplasms; Rivaroxaban; Thrombosis

Antiphospholipid syndrome (APS) is a common acquired thrombophilia associated with a high thrombotic risk, in which vitamin K antagonists (VKA) represent the mainstay of therapy. Case series involving up to 35 patients with APS suggested limited efficacy and safety of direct oral anticoagulants (DOACs).. In the prospective case series we followed 56 consecutive patients with APS (44 women and 12 men, aged from 22 to 64years), including 33 (60%) associated with systemic lupus erythematosus (SLE) and 16 (28.6%) with triple APS who were treated with DOACs due to their preferences or unstable anticoagulation with VKA. DOACs were started at least 3months since the thromboembolic event in patients with D-dimer below 500ng/ml.. Forty-nine (87.5%) patients were treated with rivaroxaban, 4 (7.3%) with dabigatran and 3 (5.4%) with apixaban. During follow-up of 2 to 43 (mean 22) months, 6 (10.7%, 5.8 per 100 patient-years) patients (4 women and 2 men, 4 with triple positive APS) experienced recurrent thrombosis, including deep vein thrombosis (n=4, including 2 episodes preceded by nonadherence), superficial vein thrombosis (n=1) and non-ST elevation myocardial infarction (n=1). The recurrence rate of VTE on DOACs was 5.8 per 100 patient-years. Two patients (3.6%) experienced severe bleeding.. This case-series suggests that DOACs are safe in patients with APS. These findings need to be confirmed in larger studies.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Vitamin K; Young Adult

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

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

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

Every year, nearly 250000 atrial fibrillation patients require temporary interruption of anticoagulation therapy for invasive procedures, acute illness, or bleeding events. Rivaroxaban is an oral anticoagulant that works by inhibiting factor Xa leading to a blockage of thrombin production, which inhibits platelet aggregation and thrombus formation. As with other anticoagulants, there is an increased risk of a thrombotic event occurring when rivaroxaban therapy is temporarily interrupted (TI) or prematurely discontinued. The 30-day rate of stroke or systemic embolism for rivaroxaban TI is 0.36%. Possible factors for higher than expected rates of embolic events include a prothrombotic perioperative environment among patients having TI for surgery and a prothrombotic environment associated with TI due to bleeding. The ROCKET AF study showed that there was no detectable difference in the risk of stroke and systemic embolism for participants treated with rivaroxaban vs warfarin undergoing TI. Another analysis suggested that the risk for stroke from TI is probably higher in the rivaroxaban group with 3 to 30 days discontinuation. Alternative anticoagulation therapy such as bridging should always be considered when stopping rivaroxaban.

Topics: Aged; Atrial Fibrillation; Factor Xa Inhibitors; Heart Atria; Heart Diseases; Humans; Male; Pericardiocentesis; Rivaroxaban; Stroke; Thrombectomy; Thrombosis

The current treatment for antiphospholipid syndrome (APS) with thrombotic manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are usually the agents of choice. However, VKA limitations, such as unpredictable anticoagulation effects due to interaction with diet and other drugs, require regular monitoring. This may impact on patients' quality of life. Since the approval of new oral anticoagulants (NOAC) for non-valvular atrial fibrillation and deep vein thrombosis prevention, much has been speculated about its use in APS patients. We report here a series of eight APS patients with failure of thrombotic prevention during rivaroxaban use. All patients had venous thrombosis as the initial manifestation of APS, and two of them also had arterial manifestations. Three patients had triple antibody positivity. Five patients developed arterial events during the treatment with rivaroxaban. Until the results of ongoing trials of rivaroxaban for APS are presented, NOAC should not be recommended to APS patients. Our preliminary experience as well cases previously reported in the literature suggest that there is a high-risk group that is less protected with rivaroxaban, namely those with previous arterial thrombosis or triple positivity. VKA remains to be the mainstay treatment for thrombotic APS.

Topics: Adolescent; Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis

We report a case of superior mesenteric artery thrombosis after the abrupt discontinuation of rivaroxaban in a 59-year-old male patient. The initial presentation was of sudden onset abdominal pain, nausea, vomiting, diarrhea, and hematochezia in the setting of recently holding rivaroxaban anticoagulation for an atrial flutter ablative procedure. Imaging revealed thrombosis of the superior mesenteric artery and acute mesenteric ischemia requiring emergent surgical intervention for embolectomy. Upon exploratory laparotomy, the bowel was found to be viable, and an embolectomy with patch angioplasty was successful without complication. This case illustrates the need for emergency medicine clinician familiarity with this possible medication adverse event with rivaroxaban.

Topics: Factor Xa Inhibitors; Humans; Male; Mesenteric Artery, Superior; Mesenteric Ischemia; Middle Aged; Rivaroxaban; Thrombosis; Withholding Treatment

The aim of this study was to describe a case series of patients with primary or secondary antiphospholipid syndrome (APS) treated with direct oral anticoagulants (DOACs).. Clinical charts of eight patients with thrombotic primary or secondary APS treated with direct oral anticoagulants (DOACs) between January 2012 and May 2015 were reviewed.. The mean age was 45 ± 14.36 (range 27-69 years). Four patients had secondary APS (50%). All patients were initially treated with warfarin by a mean time of 70.87 ± 57.32 months (range 17-153 months). Changes in anticoagulation were defined by recurring thrombosis in five patients (62.5%) and life-threatening bleeding in the other three cases. Seven patients (87.5%) received rivaroxaban treatment and one patient (12.5%) apixaban. The mean follow-up period with DOACs was 19 ± 10.06 months (range 2-36 months). There was no recurrence of thrombosis by the time of data collection.. Despite not being the standard treatment in APS, we propose DOACs as a rational alternative for the management of patients with this diagnosis. Further interventional clinical studies are necessary for possible standardization of this therapy in APS patients.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Female; Follow-Up Studies; Hemorrhage; Humans; Middle Aged; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

The authors present the history of a 62-year-old man on continuous rivaroxaban therapy who was scheduled for pulmonary vein isolation due to persistent atrial fibrillation. Preoperative transesophageal echocardiography detected the presence of left atrial appendage thrombus. Thrombophilia tests showed that the patient was heterozygous carrier of the methylene-tetrahydrofolate reductase gene mutation. The authors hypothesized that a direct thrombin inhibitor might exert a more appropriate effect against thrombosis in this case and, therefore, a switch to dabigatran was performed. After two months of anticoagulation with the direct thrombin inhibitor and folic acid supplementation the thrombus resolved. The authors underline that thrombus formation may develop in atrial fibrillation even if the patient is adequately treated with rivaroxaban. This case suggests, that methylene-tetrahydrofolate reductase gene mutation may modulate the efficacy of direct Xa factor inhibitors. According to this case history, dabigatran may be an effective therapeutic option in resolving established thrombus.

Topics: Antithrombins; Atrial Appendage; Atrial Fibrillation; Dabigatran; Echocardiography, Transesophageal; Factor Xa Inhibitors; Heart Diseases; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Rivaroxaban; Thrombosis; Treatment Outcome

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

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

To 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

Transesophageal echocardiography (TEE) is recommended in patients undergoing atrial fibrillation (AF) ablation, but use of this strategy is variable.. To evaluate whether TEE is necessary before AF ablation in patients treated with novel oral anticoagulants (NOACs).. We performed a prospective multicenter registry of AF patients undergoing radiofrequency catheter ablation on uninterrupted NOACs (apixaban and rivaroxaban). All patients were on NOACs for at least 4 weeks before ablation. Heparin bolus was administered to all patients before transseptal catheterization to maintain a target activated clotting time above 300 seconds. A subset of 86 patients underwent brain diffuse magnetic resonance imaging (dMRI) to detect silent cerebral ischemia (SCI).. A total of 970 patients (514 [53%] apixaban patients and 456 [47%] rivaroxaban patients) were enrolled for this study. The mean age was 69.5 ± 9.0 years, with 824 patients (85%) having nonparoxysmal AF, and 636 patients (65.6%) were male. The average CHA2DS2-VASc score was 3.01 ± 1.3 and CHADS2 score was ≥2 in 609 patients (62.8%). Intracardiac echocardiogram ruled out left atrial appendage thrombus in all patients whose left atrial appendage was visualized (692, 71%), and detected "smoke" in 407 patients (42%). SCI at postprocedure dMRI was detected in 2.3% (2/86). One thromboembolic event (transient ischemic attack) (0.10%) with positive dMRI occurred in a patient on uninterrupted rivaroxaban with longstanding persistent AF.. Our study illustrates that performing AF ablation while on uninterrupted apixaban and rivaroxaban without TEE is feasible and safe. This finding has important clinical and economic relevance.

Topics: Aged; Atrial Appendage; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Catheter Ablation; Echocardiography, Transesophageal; Factor Xa Inhibitors; Feasibility Studies; Female; Humans; Male; Middle Aged; Patient Safety; Preoperative Care; Pyrazoles; Pyridones; Registries; Rivaroxaban; Thrombosis; United States

Topics: Aged; Atrial Fibrillation; Catheter Ablation; Computed Tomography Angiography; Female; Humans; Recurrence; Rivaroxaban; Substance Withdrawal Syndrome; Thrombosis; Treatment Outcome

A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs.

Topics: Anticoagulants; Blood Coagulation Tests; Dabigatran; Drug Monitoring; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Neoplasms; Partial Thromboplastin Time; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Warfarin

Factor Xa (FXa) plays a significant role in the blood coagulation cascade and it has become a promising target for anticoagulation drugs. Three oral direct FXa inhibitors have been approved by the FDA for treating thrombotic diseases. By structure-activity relationship (SAR) analysis upon these FXa inhibitors, a series of novel anthranilamide-based FXa inhibitors were designed and synthesized. According to our study, compounds 1a, 1g and 1s displayed evident FXa inhibitory activity and excellent selectivity over thrombin in in vitro inhibition activities studies. Compounds 1g and 1s also exhibited pronounced anticoagulant activities in in vitro anticoagulant activity studies.

Topics: Anticoagulants; Blood Coagulation; Crystallography, X-Ray; Drug Design; Factor Xa; Factor Xa Inhibitors; Humans; Models, Molecular; Molecular Docking Simulation; ortho-Aminobenzoates; Rivaroxaban; Structure-Activity Relationship; Thrombin; Thrombosis

Dysfunction of indwelling central venous catheters (CVC) due to tissue ingrowth or clotting is common. The study objective was to determine if the oral anticoagulant rivaroxaban (RIVA) improved CVC patency and inflammation in mice.. Polyurethane catheters (0.5cm length) were placed unilaterally into the external jugular vein (EJV) of mice, which subsequently underwent daily gavage with either vehicle or RIVA (5mg/kg). CVC patency, as assessed by B-mode and Doppler ultrasound, and hematocrit were measured at 3, 7, 14 or 21days (n=8-11 mice/group/time-point). Plasma monocyte chemotactic protein-1 (MCP-1) levels were assessed by ELISA, EJV matrix metalloproteinase-9 (MMP-9) levels by western immunoblotting, and cell proliferation (anti-Ki67), macrophage infiltration (anti-MAC387) by immunostaining of EJV tissues.. CVC patency was significantly improved in RIVA-treated mice compared to vehicle-treated (93.8% vs. 62.9%) with the probability of patency in RIVA-treated mice being 1.5 times that in vehicle-treated (relative risk [RR], 1.50, 95% confidence interval [CI], 1.14-1.95, p=0.002). Plasma MCP-1 levels were lower in RIVA-treated mice vs. vehicle-treated at 21days (389±260 vs. 804±292ng/mL, p=0.005). Cell proliferation was less at day 7 in EJV from the RIVA-treated mice than vehicle-treated (5.0%±3.0 vs. 11.5%±3.6, p=0.0006), as were MMP-9 protein levels. There were no differences in hematocrit between vehicle and RIVA-treated groups at any time point. In conclusion, these data indicate RIVA lowers inflammation and improves CVC patency in a mouse model, supporting future studies to assess RIVA for improving CVC patency in patients.

Topics: Animals; Catheterization, Central Venous; Central Venous Catheters; Chemokine CCL2; Factor Xa Inhibitors; Inflammation; Mice; Mice, Inbred C57BL; Rivaroxaban; Thrombosis; Vascular Patency

Heparin fulfills its anticoagulant action through activation of antithrombin (AT), and thus thrombosis secondary to AT deficiency can be associated with heparin resistance.. A 12-year-old girl with severe venous thrombosis was referred to us because of undetectable anti-Xa levels despite low-molecular-weight heparin therapy. Laboratory investigations revealed a homozygous AT mutation in the heparin binding site (AT Budapest III). She was subsequently treated with rivaroxaban successfully.. Heparin resistance warrants evaluation for AT deficiency. Rivaroxaban may be considered a valid anticoagulant alternative to low-molecular-weight heparin in these patients.

Topics: Antithrombin III; Antithrombin III Deficiency; Binding Sites; Child; Drug Resistance; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Thrombosis

Topics: Anticoagulants; Arthritis, Infectious; Humans; Rivaroxaban; Thrombosis

Topics: Anticoagulants; Atrial Fibrillation; Echocardiography; Humans; Male; Middle Aged; Pulmonary Veins; Rivaroxaban; Stroke; Thrombosis; Warfarin

Topics: Aged; Aspirin; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Clopidogrel; Combined Modality Therapy; Coronary Angiography; Echocardiography, Transesophageal; Factor Xa Inhibitors; Humans; Male; Platelet Aggregation Inhibitors; Rivaroxaban; Septal Occluder Device; Thrombosis; Ticlopidine; Vitamin K

Data on left atrial/left atrial appendage (LA/LAA) thrombus resolution after non-vitamin K antagonist (VKA) oral anticoagulant treatment are scarce. The primary objective of X-TRA was to explore the use of rivaroxaban for the resolution of LA/LAA thrombi in patients with nonvalvular atrial fibrillation (AF) or atrial flutter, with the CLOT-AF registry providing retrospective data after standard-of-care therapy in this setting.. X-TRA was a prospective, single-arm, open-label, multicenter study that investigated rivaroxaban treatment for 6 weeks for LA/LAA thrombus resolution in patients with nonvalvular AF or atrial flutter and LA/LAA thrombus confirmed at baseline on a transesophageal echocardiogram (TEE). CLOT-AF retrospectively collected thrombus-related patient outcome data after standard-of-care anticoagulant treatment for 3 to 12 weeks in patients with nonvalvular AF or atrial flutter who had LA/LAA thrombi on TEE recorded in their medical file.. In X-TRA, patients were predominantly (95.0%) from Eastern European countries. The adjudicated thrombus resolution rate was 41.5% (22/53 modified intention-to-treat [mITT] patients, 95% CI 28.1%-55.9%) based on central TEE assessments. Resolved or reduced thrombus was evident in 60.4% (32/53 mITT patients, 95% CI 46.0%-73.6%) of patients. In CLOT-AF, the reported thrombus resolution rate was 62.5% (60/96 mITT patients, 95% CI 52.0%-72.2%) and appeared better in Western European countries (34/50; 68.0%) than in Eastern European countries (26/46; 56.5%).. X-TRA is the first prospective, multicenter study examining LA/LAA thrombus resolution with a non-VKA oral anticoagulant in VKA-naïve patients or in patients with suboptimal VKA therapy. Rivaroxaban could be a potential option for the treatment of LA/LAA thrombi.

Topics: Aged; Aged, 80 and over; Atrial Appendage; Atrial Fibrillation; Atrial Flutter; Echocardiography, Transesophageal; Factor Xa Inhibitors; Female; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Prospective Studies; Registries; Retrospective Studies; Rivaroxaban; Thrombosis

Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban.. Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Complement Activation; Factor Xa; Factor Xa Inhibitors; Female; Humans; Inflammation; International Normalized Ratio; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Warfarin

Topics: Antiphospholipid Syndrome; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

Contemporary rates of oral anticoagulant (OAC) therapy and associated outcomes among patients undergoing percutaneous coronary intervention (PCI) have been poorly described.. Using data from an integrated health care system from 2009 to 2014, we identified patients on OACs within 30 days of PCI. Outcomes included in-hospital bleeding and mortality. Of 9566 PCIs, 837 patients (8.8%) were on OACs, and of these, 7.9% used non-vitamin K antagonist agents. OAC use remained stable during the study (8.1% in 2009, 9.0% in 2014; P=0.11), whereas use of non-vitamin K antagonist agents in those on OACs increased (0% in 2009, 16% in 2014; P<0.01). Following PCI, OAC-treated patients had higher crude rates of major bleeding (11% versus 6.5%; P<0.01), access-site bleeding (2.3% versus 1.3%; P=0.017), and non-access-site bleeding (8.2% versus 5.2%; P<0.01) but similar crude rates of in-hospital stent thrombosis (0.4% versus 0.3%; P=0.85), myocardial infarction (2.5% versus 3.0%; P=0.40), and stroke (0.48% versus 0.52%; P=0.88). In addition, prior to adjustment, OAC-treated patients had longer hospitalizations (3.9±5.5 versus 2.8±4.6 days; P<0.01), more transfusions (7.2% versus 4.2%; P<0.01), and higher 90-day readmission rates (22.1% versus 13.1%; P<0.01). In adjusted models, OAC use was associated with increased risks of in-hospital bleeding (odds ratio 1.50; P<0.01), 90-day readmission (odds ratio 1.40; P<0.01), and long-term mortality (hazard ratio 1.36; P<0.01).. Chronic OAC therapy is frequent among contemporary patients undergoing PCI. After adjustment for potential confounders, OAC-treated patients experienced greater in-hospital bleeding, more readmissions, and decreased long-term survival following PCI. Efforts are needed to reduce the occurrence of adverse events in this population.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Anticoagulants; Atrial Fibrillation; Comorbidity; Dabigatran; Databases, Factual; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Length of Stay; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Patient Readmission; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stents; Stroke; Thrombosis; Venous Thromboembolism; Warfarin

Thrombosis of transcatheter aortic valve implantation (TAVI) is an uncommon complication that commonly occurs weeks to months following the procedure. Herein are described the details of a patient who presented with a recurrence of symptoms days after intervention with a bioprosthesis thrombosis that was successfully treated with direct oral anticoagulant (DOAC) therapy and resulted in hemodynamic improvement and resolution of symptoms. Whilst a previous trial of DOAC therapy with mechanical valves was stopped due to elevated events in comparison to warfarin, a TAVI valve may be different, and the rapid onset of action and reduced bleeding risk may be beneficial in this patient group.

Topics: Administration, Oral; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Bioprosthesis; Blood Coagulation; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemodynamics; Humans; Male; Prosthesis Design; Rivaroxaban; Thrombosis; Time Factors; Tomography, X-Ray Computed; Transcatheter Aortic Valve Replacement; Treatment Outcome

Topics: Adult; Anticoagulants; Enoxaparin; Hemorrhage; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) may be a critical condition in intensive care patients. Diagnosis of HIT is often difficult, and management too, as physicians have usually a limited experience with alternative anticoagulants. A 36-year-old man was admitted for orthopaedic surgery after a trauma causing a fracture of the sacrum and right ankle. Anticoagulant prophylaxis was made by nadroparin (3800  IU/day). But the patient developed less than 10 days after nadroparin exposure a significant drop in platelet count. The diagnosis of HIT was based on the pretest clinical score and demonstration of platelet factor 4 and heparin antibodies. Fondaparinux was transiently administered but was replaced 3 days later by rivaroxaban (15  mg twice a day during 21 days then 20  mg/day), after the demonstration of an acute thrombosis of the left radial artery. Platelet count returned to normal range and a partial recanalization of arterial thrombosis was noted. The use of rivaroxaban in this indication is of theoretical interest but requires further experience.

Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Heparin; Humans; Male; Morpholines; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis

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

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

The generation of thrombin in time is the combined effect of the processes of prothrombin conversion and thrombin inactivation. Measurement of prothrombin consumption used to provide valuable information on hemostatic disorders, but is no longer used, due to its elaborate nature.. Because thrombin generation (TG) curves are easily obtained with modern techniques, we developed a method to extract the prothrombin conversion curve from the TG curve, using a computational model for thrombin inactivation.. Thrombin inactivation was modelled computationally by a reaction scheme with antithrombin, α(2) Macroglobulin and fibrinogen, taking into account the presence of the thrombin substrate ZGGR-AMC used to obtain the experimental data. The model was validated by comparison with data obtained from plasma as well as from a reaction mixture containing the same reactants as plasma.. The computational model fitted experimental data within the limits of experimental error. Thrombin inactivation curves were predicted within 2 SD in 96% of healthy subjects. Prothrombin conversion was calculated in 24 healthy subjects and validated by comparison with the experimental consumption of prothrombin during TG. The endogenous thrombin potential (ETP) mainly depends on the total amount of prothrombin converted and the thrombin decay capacity, and the peak height is determined by the maximum prothrombin conversion rate and the thrombin decay capacity.. Thrombin inactivation can be accurately predicted by the proposed computational model and prothrombin conversion can be extracted from a TG curve using this computational prediction. This additional computational analysis of TG facilitates the analysis of the process of disturbed TG.

Topics: alpha-Macroglobulins; Antithrombins; Blood Coagulation; Blood Coagulation Tests; Computational Biology; Computer Simulation; Enoxaparin; Factor Xa Inhibitors; Fibrinogen; Humans; Models, Biological; Prothrombin; Reproducibility of Results; Rivaroxaban; Thrombin; Thrombosis; Time Factors

Topics: Atrial Fibrillation; Bipolar Disorder; Electroconvulsive Therapy; Factor Xa Inhibitors; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis

Direct oral anticoagulants (DOACs) are effective for stroke prevention in nonvalvular atrial fibrillation (AF). Cardioversion (CV) is frequently performed in patients with AF or flutter. To further explore the safety profile of DOACs in the context of CV, we sought to assess the prevalence of intracardiac thrombi under DOAC therapy in comparison with treatment with vitamin K antagonists. A total of 672 transesophageal echocardiograms performed in 643 patients with a history of nonvalvular AF were analyzed. The median CHA2DS2-VASc score was 4. Cases were stratified according to anticoagulation with dabigatran (n = 79), rivaroxaban (n = 122), phenprocoumon (n = 180), or bridging therapy (n = 287). In a subgroup analysis, only patients receiving phenprocoumon with an international normalized ratio ≥2 on the day of the investigation or on DOAC therapy for ≥3 weeks were considered. The prevalence of intracardiac thrombi under phenprocoumon was significantly higher than under DOACs (phenprocoumon, 17.8%; all DOACs, 3.9%; dabigatran, 3.8%; rivaroxaban, 4.1%) and showed no significant difference to bridging therapy (12.5%). In patients with sufficient short-term anticoagulation, similar differences between DOAC and phenprocoumon groups were observed (phenprocoumon, 18.4%; all DOACs, 3.8%; dabigatran, 0%; rivaroxaban, 6.6%). The influence of anticoagulation medication on thrombus rates was confirmed after adjusting for baseline intergroup differences regarding left atrial size and CHA2DS2-VASc score. In conclusion, the prevalence of intracardiac thrombi was lower under DOAC therapy than under phenprocoumon in this high-risk patient cohort. Safety of CV during DOAC treatment requires further prospective evaluation.

Topics: Aged; Anticoagulants; Arrhythmias, Cardiac; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Electric Countershock; Female; Humans; Male; Middle Aged; Morpholines; Phenprocoumon; Prevalence; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Topics: Administration, Oral; Aged; Anticoagulants; Female; Humans; Male; Middle Aged; Rivaroxaban; Short Bowel Syndrome; Thrombosis

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Electrocardiography; Factor Xa Inhibitors; Female; Humans; Phenindione; Rivaroxaban; Thrombosis; Vitamin K

Rivaroxaban can affect lupus anticoagulant (LA) testing and antiphospholipid antibodies (aPL) may interfere with the anticoagulant action of rivaroxaban.. To establish the influence of rivaroxaban on LA detection and of aPL on the anticoagulant action of rivaroxaban.. Rivaroxaban and 52 IgG preparations (20 LA+ve, 12 LA-ve thrombotic antiphospholipid syndrome [APS] patients, and 20 normal controls [NC]) were spiked into pooled normal plasma (PNP) for relevant studies. LA detection was also studied in APS patients receiving rivaroxaban 20 mg once daily.. In vitro spiking of samples with rivaroxaban showed no false positive LA with Textarin time, Taipan venom time/Ecarin clotting time (TVT/ECT), dilute prothrombin time (dPT) and in-house dilute Russell's viper venom time (DRVVT), but false positives in the majority of NC and LA negative IgG with two commercial DRVVT reagents at 250 ng/mL but not 50 ng/mL rivaroxaban. Ex vivo studies: six LA+ve patients on rivaroxaban remained LA positive with TVT/ECT and DRVVT at peak (162-278 ng/mL) and trough (30-85 ng/mL) rivaroxaban levels. Six LA-ve patients became (apparently) LA+ve with two DRVVT reagents (test/confirm ratio median [confidence interval], 1.6 [1.3-1.8], 1.6 [1.4-1.9]) but not with TVT/ECT at peak rivaroxaban levels, and remained LA-ve with both DRVVT reagents and TVT/ECT at trough levels. aPL positive IgG spiking of PNP had no effect on rivaroxaban's anticoagulant action on thrombin generation or rivaroxaban anti-Xa levels.. The TVT/ECT ratio and Textarin time were not affected even at peak rivaroxaban levels, enabling detection of LA ex vivo. aPL had no effects on rivaroxaban's anticoagulant action in vitro.

Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Factor Xa Inhibitors; False Positive Reactions; Humans; Immunoglobulin G; Lupus Coagulation Inhibitor; Predictive Value of Tests; Reproducibility of Results; Rivaroxaban; Thrombosis; Treatment Outcome

The prescription of the oral anticoagulant rivaroxaban to prevent thromboembolic episodes associated with orthopaedic surgery has dramatically increased since it was introduced. Rivaroxaban is beeing prescribed although recent in-vitro studies revealed that it impaired osteoblast metabolism. In this study we analysed the effect of rivaroxaban on fracture healing in a rat femur fracture model.. Femur fractures were created by a 3-point-bending device in 48 Wistar rats and subsequently stabilized by intramedullary nailing. After the surgical procedure animals were randomised into four groups. Two groups were fed with 3 mg rivaroxaban per kg body weight per day and two control groups were fed with chow only. Animals were euthanized 28 or 49 days after surgical procedure. Femurs underwent undecalcified histologic staining micro CT scanning and biomechanical testing. The statistical significance was evaluated using one-way Anova with Bonferroni correction.. Micro CT-scans revealed significantly increased volume of bone tissue in the fracture zone between day 28 and 49. During the same time callus volume decreased significantly. Comparing the fracture zone of the rivaroxaban group to the control group the treated group revealed a larger callus and a marginal increase of the tissue mineral density. The torsional rigidity was not influenced by the treatment of rivaroxaban.. In the present study we were able to demonstrate that rivaroxaban does not impair fracture healing in a rat femur fracture model. Considering the fact that low molecular weight heparins delay fracture healing significantly, rivaroxaban might be an improved alternative.

Topics: Animals; Anticoagulants; Biomechanical Phenomena; Bone Density; Female; Femoral Fractures; Femur; Fracture Fixation, Intramedullary; Fracture Healing; Models, Animal; Rats; Rats, Wistar; Rivaroxaban; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome

Topics: Coronary Disease; Factor Xa Inhibitors; Female; Humans; Male; Percutaneous Coronary Intervention; Postoperative Complications; Rivaroxaban; Thrombosis

Topics: Anticoagulants; Coronary Artery Bypass; Factor Xa Inhibitors; Graft Occlusion, Vascular; Heparin; Humans; Male; Middle Aged; Morpholines; Off-Label Use; Platelet Count; Radiography; Rivaroxaban; Saphenous Vein; Thiophenes; Thrombocytopenia; Thrombosis; Treatment Outcome

Topics: Carcinoma; Factor Xa Inhibitors; Heart Diseases; Humans; Kidney Neoplasms; Male; Middle Aged; Rivaroxaban; Thrombosis

The aim of this study was to improve knowledge of what happens in the coagulation of orthopaedic patients under rivaroxaban and apixaban, in order to finalize and cross-validate effective measurement methods and to provide arguments for helping to reference one or the other drug in our central pharmacy. One hundred and two patients undergoing total hip or knee replacement were included. Half of them received rivaroxaban and the other half received apixaban. Blood samples (n = 244 with each drug) were taken at Cmax preoperatively and twice a week, apart from the day of the patient's discharge, when Ctrough concentration was targeted. Routine coagulation parameters, and functional and liquid chromatography tandem mass spectrometry assays for measurement of circulating concentrations were studied. The LC-MS/MS assay and the functional assays carried out in patients under routine conditions were highly correlated, apart from low concentrations (<30 ng/ml), which were affected by the variable individual potential to inhibit the exogenous bovine Xa used in the functional assays. After 1 week of treatment, the drugs differed: Cmax and Ctrough were closer when apixaban was taken twice daily (83 ± 39 and 58 ± 17 ng/ml) than with rivaroxaban taken once a day (113 ± 67 and 13 ± 20 ng/ml). Rivaroxaban had a greater influence on routine coagulation tests and reduced the maximum thrombin concentration more efficiently, as assessed by the thrombin generation test. Although rivaroxaban and apixaban present apparently similar constant rates, they exhibit significant differences in their concentrations and anticoagulant effects when studied ex vivo in orthopedic patients.

Topics: Aged; Aged, 80 and over; Animals; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Coagulation Tests; Cattle; Chromatography, Liquid; Drug Administration Schedule; Factor Xa; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Tandem Mass Spectrometry; Thrombin; Thrombosis

The use of oral anticoagulation or dual antiplatelet therapy (DAPT) is recommended within the first 45 days after left atrial appendage (LAA) closure using the Watchman device because of incomplete device endothelialization. This study reports for the first time the feasibility of novel oral anticoagulants (NOAC) in these patients.. NOAC therapy is safe and effective after LAA closure.. Interventional LAA closure was performed successfully in 45 patients. Of these, 18 patients received NOAC during the first 45 days after implantation and 27 patients received DAPT. Transesophageal echocardiography was conducted 45 days after implantation. The primary study endpoint was abnormal thrombus apposition 45 days after implantation. Secondary study endpoints were death from any cause, major adverse cardiac and cerebrovascular events (MACCE), and major bleedings.. After 45 days, transesophageal echocardiography revealed no abnormal thrombus apposition. During a follow-up of 417 ± 323 days, 7 patients died. No stroke or transient ischemic attack occurred. Nonfatal myocardial infarction occurred in 1 patient. There was a nonsignificant trend for lower all-cause mortality (P = 0.159) and occurrence of MACCE (P = 0.096) in the NOAC group compared with the DAPT group. Overall, 6 patients suffered from a major bleeding (NOAC, n = 3; DAPT, n = 3). In NOAC group, major bleedings (at day 205, 688, and 736) occurred long after termination of NOAC therapy. There was no significant difference in the frequency of major bleedings in different groups.. Our pilot study suggests that NOAC therapy within the first 45 days after interventional LAA closure is safe and effective.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Cardiac Surgical Procedures; Dabigatran; Echocardiography, Transesophageal; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Retrospective Studies; Rivaroxaban; Stroke; Survival Rate; Thrombosis; Treatment Outcome

We herein report a case presenting with cerebral venous sinus thrombosis (CVST) associated with primary antiphospholipid syndrome (APS). The patient developed recurrent CVST followed by a hemorrhagic ischemic stroke despite the use of warfarin during the appropriate therapeutic window. Thus, we substituted warfarin to rivaroxaban with prednisolone and obtained a good clinical course. In addition to the effect of prednisolone of inhibiting elevated lupus anticoagulants and the recurrence of arterial thrombosis, rivaroxaban may prevent CVST and inhibit hypercoagulability induced by corticosteroids. The combination of an anti-Xa inhibitor and corticosteroid may be an alternative treatment for CVST and arterial thrombus with warfarin-resistant APS.

Topics: Adrenal Cortex Hormones; Anticoagulants; Antiphospholipid Syndrome; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Male; Middle Aged; Rivaroxaban; Stroke; Thrombosis; Venous Thromboembolism; Warfarin

The blood coagulation enzyme factor Xa (FXa) is a particularly promising target for anticoagulant therapy, and identification of oral small-molecule inhibitors of FXa remains a research focus. On the basis of the X-ray crystal structure of FXa and its inhibitor rivaroxaban, we designed and synthesized a series of conformationally restricted mimics containing a novel [6,6,5] tricyclic fused oxazolidinone scaffold. Intensive structure-activity relationship (SAR) and structure-pharmacokinetic relationship (SPR) studies on this new series led to the discovery of compound 11a: a highly potent, selective, direct, and orally bioavailable FXa inhibitor with excellent in vivo antithrombotic efficacy and preferable pharmacokinetic profiles. Druggability evaluation of compound 11a was undertaken and elicited positive outcomes. All results indicate that compound 11a is a promising drug candidate for the prevention and treatment of thromboembolic diseases in venous and arterial systems.

Topics: Administration, Oral; Animals; Biological Availability; Blood Coagulation; Chemistry Techniques, Synthetic; Drug Design; Factor Xa; Factor Xa Inhibitors; Oxazolidinones; Rats; Structure-Activity Relationship; Thrombosis

Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s(-1). Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM) potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG) assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT) and moderately reduce peak height (PH) of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy.

Topics: Adenosine Triphosphate; Adult; Anticoagulants; Antithrombins; Aspirin; Benzimidazoles; beta-Alanine; Blood Platelets; Dabigatran; Dose-Response Relationship, Drug; Factor Xa; Factor Xa Inhibitors; Female; Fibrin; Humans; Lab-On-A-Chip Devices; Male; Microscopy, Confocal; Morpholines; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Rivaroxaban; Thiophenes; Thrombin; Thromboplastin; Thrombosis

We report a case of a nonvalvular atrial fibrillation (NVAF) patient with acute cardioembolic stroke in whom rivaroxaban, an oral direct factor Xa inhibitor, reduced a smoke-like echo in the left atrium and resolved a thrombus in the left atrial appendage. A 71-year-old man was admitted because of the sudden onset of right hemiplegia and aphasia and was diagnosed with acute cardioembolic stroke associated with NVAF. The patient had not been treated with warfarin before admission, and rivaroxaban therapy (15 mg once daily) was initiated. Transesophageal echocardiography was performed on day 8 and a mobile thrombus was found in the left atrial appendage, accompanied by a remarkable smoke-like echo in the left atrium. Notably, the thrombus was resolved and the smoke-like echo was reduced on day 40. No recurrent ischemic stroke occurred. We describe favorable effects of rivaroxaban on the reduction of a smoke-like echo and on the resolution of a thrombus in the left atrium in an NVAF patient with acute cardioembolic stroke.

Topics: Aged; Echocardiography, Transesophageal; Embolism; Factor Xa Inhibitors; Heart Atria; Humans; Male; Morpholines; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Treatment Outcome

Intracardiac thrombus is a potentially life-threatening condition, with a high risk of embolic complications. Although vitamin K antagonists have been traditionally used for the treatment of intracardiac thrombus, they have relevant disadvantages that limit their use. Rivaroxaban is a once daily oral anticoagulant, currently indicated for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, and for the prevention and treatment of venous thromboembolism. We present the case of a 78-year-old man with nonvalvular atrial fibrillation, heart failure and creatinine clearance of 40 ml/min, anticoagulated with rivaroxaban 15 mg/day as the patient had very difficult access to hematologic controls. The transthoracic echocardiogram showed dilated left ventricle, severe left ventricular dysfunction and two images of thrombus, which disappeared after 4 weeks of treatment with rivaroxaban. To our knowledge, this is the first case reported regarding the resolution of left ventricular thrombosis with rivaroxaban.

Topics: Aged; Dose-Response Relationship, Drug; Echocardiography; Factor Xa Inhibitors; Follow-Up Studies; Heart Diseases; Heart Ventricles; Humans; Male; Morpholines; Rivaroxaban; Thiophenes; Thrombosis

Topics: Acute Coronary Syndrome; Adult; Humans; Male; Pacemaker, Artificial; Rivaroxaban; Thrombosis; Treatment Outcome

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

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

Topics: Atrial Flutter; Catheter Ablation; Coronary Angiography; Drug Monitoring; Echocardiography, Transesophageal; Electrophysiologic Techniques, Cardiac; Factor Xa Inhibitors; Heart Atria; Heart Failure; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Treatment Outcome

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Monitoring; Hemorrhage; Heparin; Humans; Morpholines; Pharmacovigilance; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis; Warfarin

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Female; Humans; Male; Morpholines; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Thrombosis; Treatment Outcome

Topics: Aged; Anticoagulants; Atrial Appendage; Factor Xa Inhibitors; Female; Heart Diseases; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Tomography, X-Ray Computed; Vitamin K

Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily were investigated to measure activities of clotting factor II, V, VII, VIII, IX, XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants; anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies and screening tests for von Willebrand disease (VWD). Two hours after rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban. Specific haemostasis clotting tests should be performed directly prior to rivaroxaban intake. Assay optimisation in the presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays are not influenced by rivaroxaban, while chromogenic assays can be used, when they do not depend on factor Xa.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Chromatography, High Pressure Liquid; Chromogenic Compounds; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Factor Xa; Factor Xa Inhibitors; False Positive Reactions; Humans; Morpholines; Nephelometry and Turbidimetry; Predictive Value of Tests; Reproducibility of Results; Rivaroxaban; Tablets; Tandem Mass Spectrometry; Thiophenes; Thrombophilia; Thrombosis; Time Factors; Treatment Outcome

Defective thrombolysis, a thrombotic risk factor, can be attributed to the formation of a compact clot poorly accessible to fibrinolytic enzymes. Venous thrombi, rich in red blood cells (RBCs), and arterial thrombi containing various amounts of RBCS, plasma and whole blood (WB) clot permeability and degradability were compared. The effect of rivaroxaban, a potent direct factor Xa inhibitor, was also evaluated.. Fibrin permeability was determined by flow measurement through the clot. Clot degradability was evaluated by the amount of D-dimer generated by clot perfusion with plasminogen and tissue plasminogen activator. Fibrin clot structure was assessed by confocal microscopy.. WB clot permeability (KS) and degradability were 6.7- and 38-fold lower, respectively, compared with plasma clots. This is attributed to 1) occlusion of fibrin pores by RBCs and 2) a consistent increase in thrombin generation due to platelets and RBCs inducing formation of a tighter clot. Rivaroxaban added to plasma or WB before clotting, in reducing thrombin generation, led to the formation of a looser clot that is more degradable by fibrinolytic enzymes. Permeability and degradability of whole blood clots formed in the presence of rivaroxaban were very similar to those of plasma clots.. The resistance to fibrinolysis of WB clots was reduced considerably when clots were formed with rivaroxaban. These results may have implications for the development of antithrombotic agents.

Topics: Anticoagulants; Blood; Blood Coagulation; Blood Platelets; Erythrocytes; Factor XIII; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Morpholines; Permeability; Plasma; Risk Factors; Rivaroxaban; Thiophenes; Thrombin; Thrombolytic Therapy; Thromboplastin; Thrombosis; Time Factors

Topics: Anticoagulants; Atrial Appendage; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Heart Diseases; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Treatment Outcome

As a potent anticoagulant agent, rivaroxaban exposes a risk of bleeding. An effective way to reverse its effects is needed. Objectives were to study efficacy and safety of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of an overdose of rivaroxaban in a rabbit model of bleeding and thrombosis.. First, a dose-ranging study assessed the minimal rivaroxaban dose that increased bleeding. Then, 48 anesthetized and ventilated rabbits were randomized into four groups: control (saline), rivaroxaban (rivaroxaban and saline), rFVIIa (rivaroxaban and rFVIIa), and PCC (rivaroxaban and PCC). The Folts model was applied: a stenosis and an injury were carried out on the carotid artery, inducing thrombosis, detected as cyclic flow reductions, which were recorded over 20 min. Then the following were measured: ear immersion bleeding time, clotting times, anti-Xa activity, thrombelastometric parameters, and thrombin generation test. Ultimately, a hepatosplenic section was performed and the total amount of blood loss after 15 min was evaluated as primary endpoint.. Rivaroxaban increased blood loss (17 g [8-32] vs. 7 g [5-18] for control (median [range]), P = 0.0004), ear bleeding time, clotting times, thrombelastographic clotting time, and decreased thrombin generation. In contrast, rFVIIa decreased ear bleeding time (92 s [65-115] vs. 140 s [75-190], P < 0.02), but without efficacy on blood loss. PCC and rFVIIa decreased activated partial thromboplastin time as well as thrombelastographic clotting time. Regarding safety, neither rFVIIa nor PCC increased cyclic flow reductions.. rFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding.

Topics: Anesthesia; Animals; Anticoagulants; Bleeding Time; Blood Coagulation Tests; Blood Pressure; Body Temperature; Dose-Response Relationship, Drug; Factor VIIa; Hemorrhage; Liver; Male; Monitoring, Physiologic; Morpholines; Prothrombin; Rabbits; Recombinant Proteins; Respiration, Artificial; Rivaroxaban; Spleen; Thiophenes; Thrombelastography; Thrombin; Thrombosis

Rivaroxaban is a potent and specific direct inhibitor of coagulation factor Xa. Recent studies have highlighted its effectiveness in the prevention of venous thrombosis and embolic stroke due to atrial fibrillation. To evaluate the antithrombotic effects of rivaroxaban in an in vivo model of arterial thrombosis, photochemical vascular injury was induced in wild-type mice by intravenous rose bengal (50 mg/kg body weight [BW]) followed by illumination of the left common carotid artery using a 543 nm helium-neon laser beam. Rivaroxaban, injected concomitantly with rose bengal at doses of 1.0, 1.5, 2.0, or 3.0 mg/kg BW, dose-dependently prolonged the times to first thrombotic occlusion and stable thrombosis. Quantitative analysis of carotid flow curves revealed higher blood volumes passing through the injured artery with increasing rivaroxaban doses (P<0.01 and P<0.001 vs. vehicle for 2.0 and 3.0 mg/kg , respectively), suggesting a dose-dependent effect on vascular patency. Consistently, a significantly higher proportion of mice that received 2.0 and 3.0 mg/kg rivaroxaban exhibited patent carotid arteries at the end of the flow monitoring period compared to vehicle alone (P<0.05 and P<0.001, respectively). Histological analysis showed complete thrombotic arterial occlusion in vehicle-treated mice compared to less thrombotic material in mice injected with 3.0 mg/kg rivaroxaban (P<0.05). Rivaroxaban also prolonged the time to cessation of tail bleeding in a dose-dependent manner, starting at 1.5 mg/kg. Similar findings were obtained in apolipoprotein E-knockout mice. Rivaroxaban may exert beneficial effects by preventing arterial thrombosis and vascular occlusion after endothelial injury.

Topics: Animals; Anticoagulants; Apolipoproteins E; Blood Coagulation; Disease Models, Animal; Factor Xa Inhibitors; Fibrinolytic Agents; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morpholines; Rivaroxaban; Thiophenes; Thrombosis

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

We evaluated the relationship between antithrombotic effects and pharmacodynamic (PD) marker changes produced by the novel factor (F)Xa inhibitors darexaban (YM150) and rivaroxaban in a rabbit model of plaque disruption-induced arterial thrombosis. Animals were subjected to catheter-induced endothelial denudation via the femoral artery followed by a two-week high-cholesterol diet. Plaque disruption was induced by balloon angioplasty, and then stasis was achieved by ligation at the distal side of the injured segment. Darexaban and rivaroxaban were administered orally 1 hour (h) before and 9 h after plaque disruption, and their antithrombotic effects were evaluated 24 h after the initiation of ligation. Prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma FXa activity were measured using blood samples collected before and 1h after administration. Darexaban and rivaroxaban significantly reduced thrombus formation. The thrombus weight obtained in the 30 mg/kg darexaban group was comparable to that in the 1 mg/kg rivaroxaban group (2.17 ± 0.63 and 3.23 ± 1.64 mg, respectively, vs. 8.01 ± 1.08 mg in the control group). Plasma FXa activity correlated with the antithrombotic effects of darexaban and rivaroxaban, while PT only correlated with those of darexaban. Our findings suggest that the degree of plasma FXa inhibition may be useful for predicting antithrombotic effects of darexaban and rivaroxaban in arterial thrombosis. PT may also be useful in evaluating antithrombotic effects of darexaban in particular.

Topics: Administration, Oral; Animals; Anticoagulants; Azepines; Benzamides; Disease Models, Animal; Factor Xa Inhibitors; Femoral Artery; Lipids; Male; Morpholines; Plaque, Atherosclerotic; Prothrombin Time; Rabbits; Rivaroxaban; Thiophenes; Thrombosis

Despite standard dual antiplatelet therapy (DAT) (acetylsalicylic acid [ASA] and clopidogrel), there is a ≥ 1.4% incidence of in-stent thrombosis in patients with acute coronary syndrome. Factor Xa inhibitors are being investigated for secondary prevention after acute coronary syndrome.. To study the antithrombotic effects of the FXa inhibitor rivaroxaban alone or in combination with DAT.. Bare metal stents (12 per animal, three per intervention period) were deployed in a porcine ex vivo arteriovenous shunt and exposed to flowing arterial blood (shear rate: 1500 s(-1)). In-stent thrombus formation was analyzed under different treatments: vehicle (n = 7 animals); intravenous (i.v.) rivaroxaban (0.11, 0.33, and 1.0 μg kg(-1) min(-1)) (n = 8); rivaroxaban + ASA (1.0 mg kg(-1) i.v.) (n = 6); rivaroxaban + ASA (1.0 mg kg(-1) i.v.) + clopidogrel (0.5 mg kg(-1) i.v.) (n = 7); and ASA (1.0 mg kg(-1) i.v.) + clopidogrel (0.5 mg kg(-1) i.v.) (n = 6).. Rivaroxaban dose-dependently reduced stent thrombus weight by ≤ 66% vs. vehicle (P < 0.05, all doses). Rivaroxaban + ASA further reduced thrombus weight vs. vehicle (86% at the highest rivaroxaban dose; P < 0.001). DAT reduced thrombus weight by ≤ 79%. However, rivaroxaban + ASA + clopidogrel almost completely abolished in-stent thrombus formation (98% reduction vs. vehicle at the highest rivaroxaban dose; P < 0.001).. Our data on the inhibitory effect of rivaroxaban alone or with DAT are consistent with the ATLAS 2 trial findings, and support its potential use for preventing stent thrombosis after stent deployment.

Topics: Animals; Aspirin; Clopidogrel; Drug Therapy, Combination; Female; Morpholines; Platelet Aggregation; Rivaroxaban; Stents; Swine; Swine, Miniature; Thiophenes; Thrombosis; Ticlopidine

Topics: Acenocoumarol; Anticoagulants; Benzamides; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thromboembolism; Thrombosis; Warfarin

A multipathway strategy was used to evaluate the in vitro and in vivo antithrombotic effects of a new synthetic family of sulfated small molecules. Polysulfated xanthonosides showed highly effective anticoagulation effects in vitro, both in plasma (clotting times) and in whole human blood (thromboelastography), as well as in vivo (ip administration, mice). Physicochemical properties were assessed for mangiferin heptasulfate (7), which showed high solubility and stability in water and in human plasma and no putative hepatotoxicity in vivo. Mangiferin heptasulfate (7) was found to be a direct inhibitor of FXa, while persulfated 3,6-(O-β-glucopyranosyl)xanthone (13) acted as a dual inhibitor of FXa (directly and by antithrombin III activation). By impedance aggregometry, compounds 7 and 13 exhibited the antiplatelet effect by inhibition of both arachidonic acid and ADP-induced platelet aggregation. Dual anticoagulant/antiplatelet agents, such as sulfated xanthonosides 7 and 13, are expected to lead to a new therapeutic approach for the treatment of both venous and arterial thrombosis.

Topics: Adult; Animals; Anticoagulants; Factor Xa Inhibitors; Glucosides; Humans; Mice; Platelet Aggregation; Platelet Aggregation Inhibitors; Sulfuric Acid Esters; Thrombosis; Xanthones

Anticoagulation with warfarin is recommended for the treatment of patients with pulmonary arterial hypertension (PAH). However, the therapeutic benefit of anticoagulation has not yet been demonstrated experimentally or clinically. Here, rivaroxaban, an oral, direct factor Xa (FXa) inhibitor, was compared with warfarin and enoxaparin in the prevention of right ventricular (RV) dysfunction and hypertrophy in the monocrotaline (MCT) model of pulmonary hypertension.. Sprague-Dawley rats (n = 10 per group) were randomized to receive rivaroxaban, warfarin, enoxaparin, or placebo before receiving a subcutaneous injection of MCT 60 mg/kg or saline. Rivaroxaban and enoxaparin were administered for 28 days starting 4 h before MCT injection; warfarin was given for 35 days initiated 7 days before MCT injection. RV haemodynamics and hypertrophy were assessed 28 days after MCT administration. Rivaroxaban dose-dependently reduced systolic and end-diastolic RV pressure increase and RV hypertrophy. Warfarin reduced RV pressure increase only. Enoxaparin had no effect on either parameter. Severe bleeding occurred in four and five rats treated with warfarin and enoxaparin, respectively, whereas no overt bleeding was observed in rats treated with rivaroxaban.. Selective, direct inhibition of FXa by rivaroxaban effectively prevented RV dysfunction and hypertrophy in MCT-injected rats, indicating a role for coagulation factors in experimental pulmonary hypertension. Clinical investigation of the impact of early and continued administration of a specific FXa inhibitor such as rivaroxaban on the course of PAH should be considered.

Topics: Animals; Blood Coagulation; Enoxaparin; Factor Xa; Factor Xa Inhibitors; Familial Primary Pulmonary Hypertension; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Morpholines; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rivaroxaban; Thiophenes; Thrombosis; Warfarin

Thromboembolism and bleeding after mechanical heart valve replacement are still unsolved problems, particularly for patients requiring anticoagulative bridging therapy. The aim of this study was to investigate whether rivaroxaban, a new oral selective and direct coagulation factor Xa inhibitor, is as effective as enoxaparin and unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves using an in vitro system. Blood from healthy male donors was anticoagulated with either UFH, enoxaparin, rivaroxaban at 300 ng/ml, (n = 10 each), or rivaroxaban at 30 ng/ml (n = 3). Mechanical aortic valve prostheses were placed into the in vitro testing system THIA II and exposed to the anticoagulant blood mixtures at a pulsatile flow for 60 min. Overall thrombus weight, coagulation parameters, and electron microscopic features of thrombus formation on the valve surface were quantified as endpoints. The mean thrombus weights were 163 ± 64 mg for group 1 (UFH), 341 ± 63 mg for the group 2 (enoxaparin), 238 ± 83 mg for group 3 (rivaroxaban 300 ng/ml) and 1.739 ± 16 mg for group 4 (rivaroxaban 30 ng/ml). Whereas high-dosed rivaroxaban showed no significant differences compared to UFH or enoxaparin, low-dosed rivaroxaban generated a massive thrombus generation, thus differing significantly from all other treatment groups regarding the thrombus weight. We hypothesize that high-dose rivaroxaban is a competitive oral available alternative to UFH and LMWH's, that might be a worthwhile alternative for patients in need of anticoagulative bridging therapy. Prospective studies have to evaluate if rivaroxaban might even overcome the limitations of OAC in patients after implantation of artificial heart valves.

Topics: Anticoagulants; Heart Valve Prosthesis; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Models, Biological; Morpholines; Perfusion; Rivaroxaban; Thiophenes; Thrombosis

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

Topics: Anticoagulants; Benzimidazoles; Carboxypeptidase B2; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Dabigatran; Fibrinolytic Agents; Humans; Morpholines; Pyridines; Receptor, PAR-1; Rivaroxaban; Thiophenes; Thrombin; Thrombomodulin; Thrombosis; Treatment Outcome; Warfarin

Topics: Blood Coagulation; Clinical Trials, Phase II as Topic; Colorimetry; Dose-Response Relationship, Drug; Drug Monitoring; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Male; Morpholines; Orthopedic Procedures; Predictive Value of Tests; Rivaroxaban; Thiophenes; Thrombosis

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Benzimidazoles; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pyridines; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis

Topics: Humans; Morpholines; Orthopedics; Postoperative Complications; Premedication; Rivaroxaban; Thiophenes; Thrombosis; Treatment Outcome

Topics: Aged; Amputation, Surgical; Anticoagulants; Arterial Occlusive Diseases; Benzimidazoles; Dabigatran; Fibrinolytic Agents; Germany; Humans; Morpholines; Peripheral Vascular Diseases; Pyridines; Rivaroxaban; Thiophenes; Thrombosis

Topics: Administration, Oral; Anticoagulants; Clinical Trials, Phase II as Topic; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K; Warfarin