rivaroxaban and Alzheimer-Disease

Alzheimer's disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear.. The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice.. In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter.. The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss.. These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia.

Topics: Alzheimer Disease; Animals; Brain Ischemia; Disease Models, Animal; Fibrinogen; Humans; Mice; Remyelination; Rivaroxaban; White Matter

Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer's disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown.. The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model.. In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model.. Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups.. The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anticoagulants; Cerebral Amyloid Angiopathy; Disease Models, Animal; Humans; Mice; Neuroinflammatory Diseases; Rivaroxaban; Warfarin

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

Topics: Aged; Alzheimer Disease; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Disease Progression; Health Care Costs; Humans; Pyrazoles; Pyridines; Pyridones; Quality-Adjusted Life Years; Rivaroxaban; Stroke; Thiazoles; Warfarin

To compare the level of adherence of public health nurses to BP measurement guidelines based on their knowledge if the guidelines and skills in BP measurement before and after Blood Pressure Measurement Training Program (BPMTP).. An experimental pre- and post-test design using two-staged cluster randomization was conducted. 118 PHNs (mean age ± 38.45 years, mean years of experience ± 13.45 years; 84.1% women) from six districts in Manila were equally assigned to either the BPMTP group or control group. Structured instruments were used.. This study showed that Blood Pressure Measurement Training Package is feasible in improving adherence of nurses based on their increased knowledge of the BP measurement guidelines and skills in BP measurement. A larger-scale study is warranted to show that BPMTP can potentially improve clinical management of hypertension in public health clinics globally.. The fixed dose of 15 mg rivaroxaban might carry a risk of under exposure, which would lead to an increase of thromboembolic complications in patients with high BMI. Therefore, rivaroxaban dose increase was suggested for obese patients. Use of DOACs appears to have considerable safety in obese patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alzheimer Disease; Angiotensin II; Animals; Antithrombins; Atrial Fibrillation; Body Mass Index; Catheter Ablation; Cohort Studies; Dabigatran; Dogs; Embolism; Factor Xa Inhibitors; Female; Genotype; Hemorrhage; Humans; Hypertension; Hypertrophy, Left Ventricular; Incidence; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Middle Aged; Norepinephrine; Obesity; Polymorphism, Single Nucleotide; Retrospective Studies; Rivaroxaban; Stroke; Sympathectomy