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Large vessel occlusion (LVO) strokes account for a significant proportion of ischemic strokes and are often cardioembolic in origin, particularly following atrial fibrillation (AF) with thrombus formation in the left atrial appendage (LAA). Although direct oral anticoagulation (DOAC) therapy reduces stroke risk in AF, anatomical and flow-related factors may still allow thrombi to form and persist, revealing the limitations of anticoagulation in high-risk patients. Examining structural and hemodynamic factors contributing to thrombus persistence is essential for optimizing patient management. We retrospectively analyzed 169 AF patients with LVO stroke who underwent cardiac CT (cCT) during acute stroke assessment. Patients were categorized based on the presence or absence of persistent LAA thrombi and further stratified by DOAC status. LAA volume, blood stasis and left ventricular (LV) diameter were measured. Thrombi were assessed using Hounsfield Unit (HU) analysis to evaluate potential differences in thrombus composition. Logistic regression analysis was performed to identify independent predictors of thrombus persistence with adjustment for DOAC therapy. Persistent LAA thrombi were identified in 23 patients (13.6%). Patients with thrombi had significantly higher rates of stasis ( = 0.004), larger left ventricular diameters ( = 0.0019) and higher LAA volumes ( = 0.004). When adjusted for DOAC therapy, larger LAA volume (OR 1.05, = 0.011), presence of LAA stasis (OR 6.14, = 0.013) and increased LV diameter (OR 1.06, = 0.006) were independent predictors of thrombus persistence. Thrombus size and HU values did not differ significantly between DOAC and non-DOAC groups. Notably, 30.4% of patients with persistent thrombi were on adequate DOAC therapy. LAA volume, stasis and LV enlargement predict thrombus persistence in the LAA of AF patients with LVO stroke, even under adequate DOAC therapy. These findings highlight the potential need for alternative antithrombotic strategies, including interventional LAA occlusion, and warrant further investigation into individualized stroke prevention in high-risk AF populations.
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http://dx.doi.org/10.3390/neurolint17080127 | DOI Listing |
J Pharm Pract
September 2025
Department of Pharmacy, Houston Methodist Hospital, TX, USA.
Critically ill adults are more commonly being admitted to intensive care units (ICU) with a recent history of direct oral anticoagulant (DOAC) use. No consensus guidance exists on optimal anticoagulation strategies in critically ill adults with non-valvular atrial fibrillation (NVAF) on DOAC's prior to ICU admission, and there is considerable variability in clinical practice. To evaluate rates of major bleeding and thrombosis between 2 anticoagulation strategies for NVAF upon ICU admission: package insert (continuation of oral or parenteral anticoagulation per manufacturer recommendations) vs non-package insert (prophylactic dosing or delayed therapeutic anticoagulation).
View Article and Find Full Text PDFJ Med Econ
September 2025
Health Economics and Outcomes Research Ltd., Cardiff, United Kingdom.
Background: Medicare plans employ drug utilization management strategies, including prior authorization (PA) and step therapy (ST), or formulary tier increases, to control spending. However, PA and ST can delay treatment access and encourage use of less effective/safe therapies, while formulary tier increases can lead to treatment switching/discontinuation due to higher patient out-of-pocket costs. This study modeled the impact of restricted access to direct oral anticoagulants (DOACs), and a tier increase for apixaban, on incidence and cost of clinical events in patients with non-valvular atrial fibrillation (NVAF) in the United States.
View Article and Find Full Text PDFEur Cardiol
August 2025
Clinical Research Centre, Sarawak General Hospital, Institute for Clinical Research, National Institutes of Health Ministry of Health Kuching, Sarawak, Malaysia.
This review explores the use of point-of-care (POC) monitoring of direct oral anticoagulants (DOACs) in patients with non-valvular AF globally and in Malaysia. As patent protection measures for innovative medicines come to an end, and generic alternatives become available, we expect a greater uptake of DOACs than warfarin by patients due to cost advantages. However, the anticoagulation effect of DOACs has been shown to vary from patient to patient and is associated with thrombotic and bleeding risks.
View Article and Find Full Text PDFDrug Des Devel Ther
September 2025
Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, 050051, People's Republic of China.
Background: Apixaban and rivaroxaban are oral direct factor Xa inhibitors, primarily eliminated through CYP3A4-mediated metabolism and direct intestinal excretion. Previous studies suggest that palbociclib, a CDK4/6 inhibitor, may increase the systemic exposure of these anticoagulants; however, the specific pharmacokinetic mechanisms remain unclear. This study aims to evaluate the effects of palbociclib on the pharmacokinetics of apixaban and rivaroxaban using a rat model to optimize combined drug regimens.
View Article and Find Full Text PDFClin Appl Thromb Hemost
September 2025
Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou of Guangdong, China.
The optimal timing for initiating direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) following acute ischemic stroke (AIS) remains a critical clinical question. This review evaluates findings from three pivotal randomized controlled trials-TIMING, ELAN, and OPTIMAS-comparing early versus delayed DOAC initiation in AF patients with AIS. Collectively, these trials provide strong evidence supporting the safety and efficacy of early initiation of DOACs in patients with AIS and AF.
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