Oral Rivaroxaban Research Articles

Anticoagulants in the treatment of superficial vein thrombosis of lower limbs: possibilities and limitations

This article presents a critical analysis of the results of three prospective randomized controlled trials of anticoagulant use in patients with superficial vein thrombosis of lower limbs CALISTO using fondaparinux sodium, STEFLUX using different doses of parnaparin sodium, and SURPRISE comparing the effectiveness and safety of fondaparinux sodium and the preventive dose of the oral anticoagulant rivaroxaban.Evidence from these clinical trials suggests that low-dose anticoagulants should be used for at least 1.5 months in superficial vein thrombosis of lower limbs with thrombus localization beyond 3 cm from the saphenofemoral and/or saphenopopliteal junction. However, anticoagulant treatment does not appear to prevent the progression of venous thrombosis after withdrawal, so in patients with persisting risk factors, it is reasonable to consider extended treatment. This seems to apply primarily to patients with superficial thrombophlebitis a history of superficial or deep venous thrombosis in the lower extremities, a family history of venous thromboembolic complications, and possibly a broader contingent of high-risk patients, not represented in the CALISTO and STEFLUX studies (with active malignancy, ongoing anticancer therapy, severe chronic heart or respiratory failure, inability to withdraw hormone replacement therapy, autoimmune disease). According to the accumulated evidence, subcutaneous injections of fondaparinux sodium, intermediate doses of low molecular weight heparin, and direct oral anticoagulant rivaroxaban in the dose of 10 mg once a day are effective and sufficiently safe in the treatment of superficial vein thrombosis of lower limbs with localization beyond 3 cm from the saphenofemoral and/or saphenopopliteal junction. Questions about the feasibility of increasing the doses of anticoagulants to further reduce the rate of superficial thrombophlebitis - progression during treatment and the optimal duration of their use remain open.

Comparison of co-administration of amiodarone and rivaroxaban to co-administration of dronedarone and rivaroxaban for hemorrhage risks after atrial fibrillation ablation

PurposeTo investigate whether co-administration of antiarrhythmic dronedarone and anticoagulant rivaroxaban would increase the risks of hemorrhage after atrial fibrillation (AF) ablation.MethodsA total of 100 patients with AF who underwent radiofrequency catheter ablation (CA) in the Department of Cardiology, the Affiliated Hospital of Qingdao University from 2019–12 to 2020–11 were included. Patients were divided into an oral dronedarone and rivaroxaban group (D-R group, N = 50) and an oral amiodarone and rivaroxaban group (A-R group, N = 50) according to the postoperative antiarrhythmic and anticoagulation strategies. Patients in 2 groups were given propensity score matching (PSM) to obtain a sample with balanced inter-group covariates. A retrospective observational study was conducted. After 3 months of follow-up, the incidence of clinically relevant non-major bleeding (CRNMB), major hemorrhages, and early AF recurrence was observed.ResultsAfter PSM, 41 patients were included in each group. With similarly distributed baseline characteristics and ablation characteristics after PSM, the CRNMB rate after AF ablation was significantly higher in the D-R group than in the A-R group (26.8% versus 7.3%, P = 0.02), and no major hemorrhages were detected in both groups. No significant difference was observed in the sinus rhythm maintenance rate between the D-R group and the A-R group (26.8% vs. 22.0%, P = 0.43).ConclusionsCompared to co-administration of amiodarone and rivaroxaban, co-administration of dronedarone and rivaroxaban increases the risk of CRNMB but it does not increase the risk of major hemorrhages in blanking period after AF ablation.

Anticoagulants after Discharge in Patients with COVID-19: What we Know at the End of 2021

This review discusses reasons for prolonged use of anticoagulants after discharge of patients with COVID-19 without additional indication for anticoagulation. Data regarding rate of thrombotic and thromboembolic complications in patients with COVID-19 after discharge from the hospital are presented. Large randomized controlled trials EXCLAIM, ADOPT, MAGELLAN, APEX and MARINER with prolonged use of anticoagulants in patients hospitalized with acute nonsurgical diseases before pandemia of COVID-19 are discussed. The first prospective randomized controlled trial MICHELLE with direct oral anticoagulant rivaroxaban in a dose 10 mg once daily after discharge of patients with COVID-19 with high risk at least venous thromboembolism are analyzed. It seems that the most relevant approach for the determination of indications for prolonged use of anticoagulants in doses dedicated for primary prevention of venous thromboembolism after discharge of patients with COVID-19 without apparent indication for anticoagulation is a modified IMPROVE VTE risk score with the addition of elevated in-hospital D-dimer level. And the most well-studied approach for anticoagulation in these patients is a direct peroral anticoagulant rivaroxaban 10 mg once daily for 35 (and possibly up to 45) days after discharge.

Renal Function Protection as an Important Component of a Comprehensive Approach to the Management of Patients with Atrial Fibrillation

The increase in the life expectancy of the population is accompanied by an increase in the prevalence of diseases for which old and senile age are risk factors. Atrial fibrillation (AF) and chronic kidney disease (CKD) are two diseases that can coexist in a patient. The risk of ac thromboembolic and hemorrhagic events in this case increases due to the mutual aggravating influence of these diseases. In addition, these patients have a high incidence of coronary events, and cardiovascular complications are the main cause of death in patients with AF and CKD. Consequently, such patients require an integrated approach to treatment, and their management is a complex clinical task. The direct oral anticoagulant rivaroxaban has been most studied in a population of comorbid AF and CKD patients and has proven a high efficacy and safety profile in these patients in randomized controlled trials. In addition, rivaroxaban has shown a significant reduction in the risk of myocardial infarction in various patients, as well as the possibility of preserving renal function to a greater extent compared with warfarin therapy, and a possible positive effect on reducing the risk of cognitive impairment. A single dosing regimen can improve adherence to treatment, which is one of the key conditions for achieving the above effects. Thus, these factors make it possible to achieve comprehensive protection of comorbid patients with AF and CKD.

Safety and Efficacy Evaluation of Antithrombotic Therapy with Rivaroxaban and Clopidogrel After PCI in Chinese Patients.

ObjectiveTo investigate the efficacy and safety of the antithrombotic therapy using the oral anticoagulant rivaroxaban and clopidogrel in Chinese patients with acute coronary syndrome complicated with atrial fibrillation after percutaneous coronary intervention.MethodsA total of 100 patients were selected. Patients were randomly divided into two groups: the treatment group (rivaroxaban group) received a therapy of rivaroxaban and clopidogrel. The control group (warfarin group) receivied a combined treatment of warfarin, clopidogrel, and aspirin. The primary outcome endpoint was evaluated based on the adverse cardiac and cerebrovascular events within 12 months.ResultsA total of 8 (8.00%) main adverse cardiac and cerebrovascular events occurred during the 12 months of follow-up, including 5 (9.80%) in the warfarin group and 3 (6.10%) in the rivaroxaban group. The risk of having main adverse cardiac and cerebrovascular events in the two groups was comparable (P = 0.479). A total of 9 patients (9.00%) were found to have bleeding events, among which 8 patients (15.7%) were in the warfarin group, whereas only 1 patient (2.00%) was in the rivaroxaban group. Therefore, the risk of bleeding in the warfarin group was significantly higher than that in the rivaroxaban group (P = 0.047).ConclusionsIn Chinese patients with acute coronary syndrome complicated with atrial fibrillation, the efficacy of the dual therapy of oral anticoagulant rivaroxaban plus clopidogrel after percutaneous coronary intervention was similar to that of the traditional triple therapy combined with warfarin, aspirin and clopidogrel, but it has a better safety property, which has potential to widely apply to antithrombotic therapy after PCI

MANAGEMENT OF TOOTH EXTRACTIONS IN PATIENTS RECEIVING THE NEW ORAL ANTICOAGULANTS

Introduction: High bleeding risk procedures pose a serious challenge for dental practitioners treating patients taking some of the novel oral anticoagulants. Aim: The aim of the present study was to assess clinically the bleeding risk in a typical tooth extraction in patients on monotherapy with one of the new oral anticoagulants rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa). Materials and methods: The study included 30 patients on these anticoagulants who underwent a typical tooth extraction. Local hemostasis was achieved using Surgicel, Haemocollagen or Gelaspon, and suturing the edges of the wound. Clinical evaluation of the bleeding was performed at 10 and 30 minutes, and 24 hours after the extraction. Anticoagulants were discontinued for the day of extraction. Results: Post-extraction bleeding in the first 10 minutes was observed in 17 patients (56.66%). Bleeding within 30 minutes was observed in 11 patients (36.66%). Two (6.66%) patients reported having only mild oozing within 24 hours. No additional haemostasis was required for any of the patients. Bleeding in a typical tooth extraction is of capillary origin. Bleeding sites are easily accessible and local hemostatic agents are effective enough to control the bleeding. Discontinuation of the anticoagulant on the day of extraction is sufficient to prevent any adverse events. No abnormal post-extraction bleeding was observed in our study. Conclusions: If tooth extraction is required in patients taking the new oral anticoagulants rivaroxaban (Xarelto), apixaban (Eliquis) or dabigatran (Pradaxa), the patient can cease the reception of the drug only for the day of the procedure.

Recalcitrant livedoid vasculopathy: A successful treatment with oral rivaroxaban

Recalcitrant livedoid vasculopathy: A successful treatment with oral rivaroxaban

Problems of adherence to treatment with oral anticoagulants in elderly patients with atrial fibrillation in the Kyrgyz Republic

Objectives assessment of adherence to treatment in elderly patients with nonvalvular atrial fibrillation who were prescribed anticoagulant therapy with vitamin K antagonist, warfarin, and a new oral anticoagulant rivaroxaban.
 Material and methods. During the study, 322 patients with atrial fibrillation of nonvalvular etiology were observed. Depending on the type of anticoagulant taken, the patients were divided into 2 groups: the first group included 253 (78.6%) people who took warfarin, the second group 69 (21.4%) people, who were prescribed a new oral anticoagulant rivaroxaban.
 Results. By the end of the one-year follow-up from the start of anticoagulant treatment, only 8.7% of patients in the first group followed the doctor's prescription; the second group had 59.4% of adherent patients. The vast majority of patients refused warfarin therapy due to the inability to control INR. In the case of the appointment of rivaroxaban, the reason for the refusal to take was the high cost of the drugs.
 Conclusion. Effective prevention of thromboembolic complications in atrial fibrillation requires the development of appropriate measures to improve adherence to treatment.

Factor Xa Inhibitors for Patients after Mechanical Heart Valve Replacement?

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.

Study on the Relationship between Rivaroxaban and Factor Xa Activity in Blood Based on HPLC-MS/MS

The aim of the study was to investigate a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of rivaroxaban and evaluate the correlation between plasma concentration and anti-Xa activity in patients using oral rivaroxaban. In this study, the plasma concentration of rivaroxaban and anti-Xa factor activities was determined in 125 patients, and the relationship between the two variables was analysed by SPSS 21.0 software. The results showed that the plasma concentrations of oral rivaroxaban patients were significantly correlated with the activity of the anti-Xa factor (Spearman's r = 0.990, P < 0.05). The plasma concentrations of rivaroxaban are a potentially useful monitoring indicator to assess the patient's bleeding risk if testing for plasma anti-Xa activity is not available.

Deep venous thrombosis in an individual with statin-exposed anti-SRP myopathy: case report and review of literature

BackgroundImmune-mediated necrotizing myopathy (IMNM) is characterized by proximal muscle weakness, elvated serum muscle enzyme levels, myopathic electromyography findings, and necrotic muscle fiber with few inflammatory cell infiltration in muscle biopsies. Statins, the first line drug to lower triglyceride and cholesterol level in blood, have been reported to be associated with statins-induced necrotizing autoimmune myopathy (SINAM). Although anti-3-hydroxy-3-methylglutarylcoenzyme-A reductase (anti-HMGCR) myopathy is considered as the leading myopathy related to the statins medication, anti-signal recognition particle (SRP) myopathy were also identified in several cases with statin exposure. The risk of deep venous thrombosis (DVT) is substantially high in individuals with autoimmune inflammatory diseases. But few studies have reported the occurrence and recommendation for treatment of DVT in patients with anti-SRP myopathy. Here, we reported a statin-exposed anti-SRP myopathy individual developed DVT who was successfully treated with catheter-directed thrombolysis (CDT) and systemic anticoagulants therapy.Case presentationA 56-year-old Chinese female came to the outpatient room with gradually progressive bilateral lower-extremity weakness. Magnetic resonance imaging revealed myopathy in bilateral thighs. Serum anti-SRP antibody was positive. She was diagnosed with anti-SRP myopathy. When treated with corticosteroids and immunosuppressants, the patient developed mild edema and pain of left lower extremity. Angiography and ultrasound revealed diffuse venous thrombosis of left lower extremity. Therapy was initiated with CDT and lower molecular weight heparin, then switched to once daily oral rivaroxaban. Meanwhile, steroids combined with tacrolimus were also carried on while simvastatin was discontinued. One month later, patient’s symptoms were resolved and only partial thrombosis in left femoral vein was remained.ConclusionThe prevalence of DVT in patient with anti-SRP myopathy was rare. No well-established treatment strategy is available to manage the IMNM and DVT at the same time. The systemic anticoagulants therapy combined CDT can be an effective therapeutic approach to address extensive DVT in patient with anti-SRP myopathy.

Abstract 10011: Oral Rivaroxaban versus Subcutaneous Enoxaparin in the Prophylaxis of Covid-19 Induced Coagulopathy in Mild to Moderate Sars Cov-2 Infection

Introduction: Preliminary data highlights the importance of anticoagulation therapy in the prevention and treatment of thromboembolism in SARS CoV-2 infection. There is insufficient data comparing the safety and efficacy of direct oral anticoagulants (DOACs) and subcutaneous enoxaparin in the prophylactic management of COVID-19 associated thromboembolic disease, particularly in mild to moderate cases of COVID-19 infection. Hypothesis: Oral rivaroxaban is superior to subcutaneous enoxaparin in the prophylaxis of COVID-19 induced coagulopathy in mild to moderate SARS CoV-2 infection. Methods: In this randomized, open-label, prospective, superiority trial involving hospitalized patients with confirmed mild or moderate COVID-19 disease, we began enrolment of 230 patients from 1 st August 2020 to receive either once-daily oral rivaroxaban (10mg or 15mg) or once-daily subcutaneous enoxaparin (40mg or 60mg) for duration of in-hospital stay (median: 8 days). Patients were randomised in a 1:1 ratio into groups by computer-generated allocation software. The primary outcome was a composite of all major, clinically relevant haemorrhagic and thrombotic events. An intention-to-treat analysis was carried out on the dataset. The trial was registered with Clinical Trials Registry of India (CTRI/2021/05/033871). Results: The primary efficacy outcome occurred in 4 of 115 patients in the rivaroxaban group (3.5%) versus 16 of 113 patients in the enoxaparin group (14.2%) (hazard ratio 0.207, 95% confidence interval [CI], 0.069 to 0.621, P=0.005). Adverse events developed in 4.3% of patients in the study group and 12.4% in the enoxaparin group (hazard ratio 0.328; 95% CI, 0.118 to 0.910; P=0.032). Major bleeding was seen in 1 patient (0.9%) in the rivaroxaban group and 3 patients (2.7%) in the enoxaparin group. Conclusions: Rivaroxaban alone was superior to enoxaparin for the prophylactic management of coagulopathy associated with mild to moderate SARS CoV-2 infection.

Abstract 10233: Interruption of Perirenal Adipose Tissue Thromboinflammation Reverses Prediabetic Kidney Impairment

Introduction: Mounting evidence suggests that micro- and macrovascular complications typically seen in diabetic patients commence in prediabetes. In absence of protracted hyperglycemia and its downstream pathological pathways, alternative mechanisms contribute to the observed cardiorenal involvement. Recent work from our laboratory implicated localized adipose inflammation in the detrimental phenotype in early metabolic deterioration, where inflammatory changes in perirenal adipose tissue triggered kidney functional and vascular deterioration. Significantly, thromboinflammatory processes involving increased factor Xa activity contribute to the low-grade adipose tissue inflammation resulting in vascular remodeling, vascular injury, atherosclerosis and organ damage, acting in a positive feedback loop further exacerbating tissue damage. Hypothesis: As such, we hypothesize factor Xa inhibition in a non-obese prediabetic rat model of localized perirenal adipose inflammation will mitigate the functional and renovascular derangements associated with metabolic dysfunction. Methods: Our rat model is induced by twelve weeks of high-caloric diet feeding to evoke a non-obese normoglycemic prediabetic phenotype. Prediabetic rats received daily oral rivaroxaban (20 mg/Kg) for the last two weeks of feeding. Renal function was assessed by measuring urinary protein excretion and glomerular filtration rate. Renovascular reactivity was examined in isolated perfused kidney preparations. Markers of inflammation, oxidative stress, and structural damage were studied in perirenal adipose and renal cortices. Results: High-calorie diet induced local adipose tissue inflammation and subsequent renovascular deterioration evident by an impaired renovasular endothelial feedback. This was associated with augmented oxidative stress and interstitial fibrosis. Rivaroxaban treatment decreased markers of perirenal adipose inflammation, oxidative stress and improved kidney structure and function. Conclusion: Our results highlight a pleotropic effect of the factor Xa inhibitor, rivaroxaban, in decreasing perirenal adipose tissue inflammation and subsequent amelioration of the deteriorated kidney function in prediabetes.

Comparison of Enoxaparin and Rivaroxaban in the Prophylaxis of Deep Venous Thrombosis in Arthroplasty.

Background Pulmonary embolism is a serious early complication of arthroplasty procedures that can develop after deep venous thrombosis. The present study aimed to compare rivaroxaban and enoxaparin in terms of preventing DV and PE, and also in this study, we compared the complications due to these drugs in patients undergoing elective arthroplasty. Materials and Methods 214 patients were divided into three groups based on their treatment regimens. In group I, enoxaparin was used, in group II, rivaroxaban was used, and in group III, enoxaparin was used throughout hospitalization, and after hospital discharge, rivaroxaban was used. These three groups were compared according to the occurrence of deep venous thrombosis, pulmonary embolism, and major and minor complications. Results Major postoperative complications occurred in 5, 15, and 6 patients in group I, II, and III, respectively. Minor postoperative complications occurred in 10, 24, and 11 patients in group I, II, and III, respectively. No significant difference was found among the three groups. Deep venous thrombosis or pulmonary embolism was not observed in any patient. Conclusion Rivaroxaban was found to be as effective as enoxaparin in the prevention of deep venous thrombosis and other complications after arthroplasty. Moreover, oral rivaroxaban provided greater ease of use compared to subcutaneous enoxaparin. Based on these findings, we consider that rivaroxaban could be an effective alternative to enoxaparin.

A case series of vaccine-induced thrombotic thrombocytopenia in a London teaching hospital.

The ChAdOx1 nCoV‐19 vaccine has been associated with increased risk of thrombosis. Understanding of the management of these rare events is evolving, and currently recommended treatments include human normal immunoglobulin and nonheparin anticoagulation such as direct oral anticoagulants. Our report describes three consecutive patients presenting to a London teaching hospital with vaccine‐induced thrombotic thrombocytopenia (VITT), also referred to as vaccine‐induced prothrombotic immune thrombocytopenia. The patients ranged in age from 40 to 54 years and two had no known previous medical comorbidities. Two patients had cerebral venous sinus thrombosis and one had a deep vein thrombosis. Two were treated with anticoagulation, one with oral rivaroxaban and the other with an intravenous argotraban infusion that was later converted to oral apixaban. One patient received three doses of human normal immunoglobulin and 5 days of therapeutic plasma exchange. This case series may be used to improve understanding of the clinical course and management of VITT.

Rivaroxaban for Improvement in Thromboembolism Outcomes in Patients with Multiple Myeloma on Lenalidomide-Based Therapy: The Rithmm Feasibility Pilot Trial

Rivaroxaban for Improvement in Thromboembolism Outcomes in Patients with Multiple Myeloma on Lenalidomide-Based Therapy: The Rithmm Feasibility Pilot Trial

Aspirin versus Rivaroxaban to Prevent Venous Thromboembolism after Total Knee Arthroplasty: A Double-blinded, Randomized Controlled Trial.

Objective Aspirin (acetylsalicylic acid, ASA) and rivaroxaban are anticoagulants that have increased in popularity due to ease of use in the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA). The present study aimed to evaluate the efficacy of ASA compared with that of rivaroxaban on VTE prophylaxis in patients who underwent TKA. Method Forty patients who had primary knee osteoarthritis and would undergo TKA were randomized into two groups. In total, 20 patients in the ASA group used oral aspirin, at a dose of 300 mg/day, for VTE prophylaxis after TKA, while 20 patients in the rivaroxaban group received oral rivaroxaban, at a dose of 10 mg/day. On days 4 and 14 after the operation, deep vein thrombosis (DVT) in the lower limbs on the operated side was detected through duplex ultrasonography. Other complications were recorded for 14 days. Results There were no positive findings of DVT detected with duplex ultrasonography in the groups of patients, and the occurrence of pulmonary embolism was not observed. In total, 4 patients had subcutaneous ecchymosis on the fourth postoperative day (2 patients in the ASA group and 2 patients in the rivaroxaban group; p = 1.0), and another 4 patients on the fourteenth postoperative day (1 patient in the ASA group and 3 patients in the rivaroxaban group; p = 0.292). No cases of wound hematoma, major organ bleeding, wound infection, or reoperation were observed in the sample. Conclusion Aspirin and rivaroxaban had comparable efficacy to prevent VTE, without increasing the incidence of wound complications and bleeding after TKA.

Role of Rivaroxaban in Patients with Cerebral Venous Thrombosis

Objective: Cerebral venous thrombosis is a common neurological disease. It has been treated so far with Warfarin that needs continuous monitoring of PT (prothrombin time) and INR (International Normalization Ratio) with potential complications due to this problem. Newer oral anticoagulants have been recommended for other thromboembolic events like pulmonary embolism and can be a good alternative treatment of CVT. We determined the effectiveness of new oral anticoagulant Rivaroxaban in patients with cerebral venous thrombosis.&#x0D; Material and Methods: The study was conducted in the indoor department of Neurology, Punjab Institute of neurosciences for 1year. Magnetic cerebral venography (MRV) Brain was done at the start of Rivaroxaban, at 3 months and at 6 months where needed. The bias effect was removed by getting MRV done and reported from the same department.&#x0D; Results: A total of 18 patients were enrolled in the study. One patient was lost to followup. Mean age of our patient data was 28.66 ± 6.66. 16 (88%) patients were females and 2 (11%) were males. 9 patients (50%) had clinical and radiological recovery based on MRV brain at 3 months.7 patients (38%) had recovery based on clinical and radiological parameters at 6 months. Only 1 patient had partial recanalization but that also improved clinically.&#x0D; Conclusion: Rivaroxabancan is a very effective alternative for warfarin in cerebral venous sinus thrombosis which will avoid concerns commonly encountered with warfarin.

Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

Depression is a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression can lead to suicidal thoughts and behavior. The present study aimed to evaluate the effect of the direct oral anticoagulant rivaroxaban (RVX), in the model of depression induced by chronic unpredicted mild stress (CUMS) in rats. Fifty-six male Wister rats were randomly divided into seven experimental groups (8 rats/group); Group 1: Control group given vehicle per oral (p.o.), Group 2: RVXL-control group (received rivaroxaban 20 mg/kg/day, p.o..), Group 3: RVXH-control group (received rivaroxaban 30 mg/kg/day, p.o.), Group 4: chronic unpredictable mild stress (CUMS) group, Group 5: FLX-treated CUMS group (received fluoxetine 10 mg/kg/day, p.o..), Group 6: RVXL-treated CUMS group (received rivaroxaban 20 mg/kg/day, p.o.), and Group 7: RVXH-treated CUMS group (received rivaroxaban 30 mg/kg/day, p.o.). The rats received the drugs from the first day of the experiment and continued till 4 weeks—the duration of the study. The following were measured: monoamine neurotransmitters, malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor‐kappa B (NF‐κB), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A). A forced swimming test (FST) was done. Furthermore, histological changes and glial fibrillary acidic protein (GFAP) immunoexpression were evaluated. CUMS showed a significant decrease in hypothalamic neurotransmitters, hippocampal GSH, SOD, BNDF, and VEGF-A with a significant increase in hippocampal MDA, NOx, NF-kβ, Myd88, TLR4, TNF-α, and GFAP immunoexpression. RVX showed significant improvement in all parameters (p -value < 0.0001). In conclusion, RVX in a dose-dependent manner possesses potent ameliorative effects against depression by reducing the oxidative stress and inflammatory process, through the regulation of the TLR4/Myd88/NF-kβ signaling pathway.

Direct Oral Anticoagulants in Patients with Obesity and Atrial Fibrillation: Position Paper of Italian National Association of Hospital Cardiologists (ANMCO).

The use of the direct oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban (DOACs) offers some major advantages over warfarin and other vitamin K antagonists (VKAs). One advantage is the possibility to use a fixed dose in normal-weight patients, overweight patients and patients with obesity. However, the “one size fits all” strategy raised a concern regarding the possibility to undertreat patients with a high body mass index. No randomized controlled trials (RCTs) have ever compared VKAs and DOACs in this population. We analyzed data from the literature on DOAC pharmacokinetics and pharmacodynamics, results from the four pivotal phase III trials on non-valvular atrial fibrillation, retrospective observational studies and metanalyses. While we are aware of the limitation imposed by the absence of specific RCTs, we propose the position of the Italian Association of Hospital Cardiologists (ANMCO) on the use of DOACs in patients with obesity based on the existing evidence.