Dataset Information

Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery.

ABSTRACT: 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.

SUBMITTER: Mastenbroek TG

PROVIDER: S-EPMC7653917 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery.

Mastenbroek T G TG Karel M F A MFA Nagy M M Chayoua W W Korsten E I J EIJ Coenen D M DM Debets J J Konings J J Brouns A E AE Leenders P J A PJA van Essen H H van Oerle R R Heitmeier S S Spronk H M HM Kuijpers M J E MJE Cosemans J M E M JMEM

Scientific reports 20201109 1

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 ...[more]

PMID: 33168914

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Project description:The Vascular Registry (VR) on carotid procedures collects long-term outcomes on carotid artery stenting (CAS) and carotid endarterectomy (CEA) patients. The purpose of this report is to describe in-hospital and 30-day CAS outcomes in patients with atherosclerotic carotid artery disease (CAD; atherosclerosis [ATH]) compared to recurrent carotid stenosis (RES) and radiation-induced stenosis (RAD).The VR collects provider-reported data on CAS using a Web-based data management system. For this report, data were analyzed at the preprocedure, procedure, predischarge, and 30-day intervals.As of November 20, 2008, there were 4017 patients with CAS with discharge data, of which 72% were due to ATH. A total of 2321 patients were available for 30-day outcomes analysis (1623 ATH, 529 restenosis, 119 radiation, 17 dissection, 3 trauma, and 30 other). Baseline demographics showed that ATH occurred in older patients (72-years-old), had the greatest history of coronary artery disease (CAD; 62%), myocardial infarction (MI; 24%), valvular heart disease (8%), arrhythmia (16%), congestive heart failure (CHF; 16%), diabetes mellitus (DM; 35%), and chronic obstructive pulmonary disease (COPD; 20%). RES had a higher degree of baseline stenosis (87.0 vs 85.8 ATH; P = .010), were less likely to be symptomatic (35.5% vs 46.3% ATH; P < .001), but had a greater history of hypertension, peripheral vascular disease (PVD), and smoking. RAD was seen in younger patients (66.6 vs 71.7 ATH; P < .001), were more likely to be male (78.2% vs 60.9% ATH; P < .001), and had less comorbidities overall, with the exception of amaurosis fugax, smoking, and cancer. The only statistically significant difference in perioperative rates was in transient ischemic attack (TIA; 2.7% ATH vs 0.9% RES; P = .02). There were no statistically significant differences in in-hospital death/stroke/MI (ATH 5.4%, RES 3.8%, RAD 4.2%) or at 30 days (ATH 7.1%, RES 5.1%, RAD 5.0%). Even after adjusting for age, gender, symptomatology, CHF, and renal failure, the only statistically significant difference at 30 days was amaurosis fugax between ATH and RAD (odds ratio [OR] 0.13; P = .01).Although patients with ATH have statistically significant comorbidities, they did not have statistically significant increased rates of death/stroke/MI during hospitalization or within 30 days after discharge when compared to RES or RAD. The CAS event rates for ATH vs RES and RAD are similar, despite prior published reports. Symptomatic ATH have statistically significant higher rates of death/stroke/MI compared to asymptomatic cohort. Finally, consistent and accurate entry of long-term data beyond initial hospitalization is essential to fully assess CAS outcomes since a significant number of adverse events occur in the interval from hospital discharge to 30 days.

Project description:BackgroundIn the management of Peripheral Arterial Disease (PAD), the administration of anticoagulant or antiplatelet agents is imperative. The use of Dual Antiplatelet Therapy (DAPT) in conjunction with rivaroxaban has shown potential in mitigating adverse outcomes. Given the heterogeneity in the pathology of lower limb arteries, there is a compelling case for individualized treatment strategies.MethodsIn a single-center retrospective study on pharmacotherapy for peripheral artery disease, patients were treated with either aspirin combined with rivaroxaban or aspirin coupled with clopidogrel. The primary efficacy outcome encompassed a composite of increases in the Rutherford classification, acute limb ischemia, amputations due to vascular causes, target lesion revascularization, myocardial infarction, ischemic stroke, and cardiovascular death. The primary safety outcome was major bleeding, as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria; meanwhile, major bleeding as categorized by the International Society on Thrombosis and Haemostasis (ISTH) served as a secondary safety outcome. The study differentiated between two subgroups: patients with only above-the-knee and below-the-knee arterial lesions.ResultsFrom January 2016 to December 2021, 455 patients received either clopidogrel plus aspirin or rivaroxaban plus aspirin following endovascular treatment (EVT). The rivaroxaban group (n = 220) exhibited a lower incidence of primary efficacy outcomes [49.1% vs. 60.4%, hazard ratio (HR) 0.77, P = 0.006] but had more TIMI major bleeding events (5.9% vs. 2.1%, HR 2.6, P = 0.04). ISTH major bleeding events did not show a significant difference, though a higher percentage of rivaroxaban patients discontinued medication due to bleeding (10% vs. 4.7%, HR 2.2, P = 0.03). In the above-the-knee arterial disease subgroup, the rivaroxaban group demonstrated a lower incidence of primary efficacy outcomes (28.2% vs. 45.2%, HR 0.55, P = 0.02). In the below-the-knee arterial disease subgroup, no significant difference was observed in the occurrence of primary efficacy events between the two groups (58.7% vs. 64.8%, HR 0.76, P = 0.14).ConclusionRivaroxaban plus aspirin improved outcomes compared to DAPT in patients with lower extremity artery disease. Similar findings were observed in the above-the-knee artery lesion-only group. However, in the below-the-knee artery lesion-only group, rivaroxaban plus aspirin did not surpass DAPT in efficacy. Regarding safety, rivaroxaban plus aspirin exhibited higher bleeding risks and more frequent treatment discontinuation than aspirin combined with clopidogrel.

Project description:BackgroundPatients with chronic coronary artery disease or peripheral artery disease and history of heart failure (HF) are at high risk for major adverse cardiovascular events. We explored the effects of rivaroxaban with or without aspirin in these patients.MethodsThe COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized 27 395 participants with chronic coronary artery disease or peripheral artery disease to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg alone. Patients with New York Heart Association functional class III or IV HF or left ventricular ejection fraction (EF) <30% were excluded. The primary major adverse cardiovascular events outcome comprised cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome was major bleeding using modified International Society of Thrombosis and Haemostasis criteria. Investigators recorded a history of HF and EF at baseline, if available. We examined the effects of rivaroxaban on major adverse cardiovascular events and major bleeding in patients with or without a history of HF and an EF <40% or ≥40% at baseline.ResultsOf the 5902 participants (22%) with a history of HF, 4971 (84%) had EF recorded at baseline, and 12% had EF <40%. Rivaroxaban and aspirin had similar relative reduction in major adverse cardiovascular events compared with aspirin in participants with HF (5.5% versus 7.9%; hazard ratio [HR], 0.68; 95% CI, 0.53-0.86) and those without HF (3.8% versus 4.7%; HR, 0.79; 95% CI, 0.68-0.93; P for interaction 0.28) but larger absolute risk reduction in those with HF (HF absolute risk reduction 2.4%, number needed to treat=42; no HF absolute risk reduction 1.0%, number needed to treat=103). The primary major adverse cardiovascular events outcome was not statistically different between those with EF <40% (HR, 0.88; 95% CI, 0.55-1.42) and ≥40% (HR, 0.81; 95% CI, 0.67-0.98; P for interaction 0.36). The excess hazard for major bleeding was not different in participants with HF (2.5% versus 1.8%; HR, 1.36; 95% CI, 0.88-2.09) than in those without HF (3.3% versus 1.9%; HR, 1.79; 95% CI, 1.45-2.21; P for interaction 0.26). There were no significant differences in the primary outcomes with rivaroxaban alone.ConclusionsIn patients with chronic coronary artery disease or peripheral artery disease and a history of mild or moderate HF, combination rivaroxaban and aspirin compared with aspirin alone produces similar relative but larger absolute benefits than in those without HF.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Dataset Information

Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery.

Publications

Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery.

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