Rivaroxaban, in combination with low-dose aspirin, is associated with a reduction in proinflammatory and prothrombotic circulating vesicle signatures in patients with cardiovascular disease.

IF 5.5 2区 医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2024-10-15 DOI:10.1016/j.jtha.2024.09.030
Luisa Weiss, Aideen O'Doherty, Wido Uhrig, Paulina B Szklanna, Molly Hong-Minh, Kieran Wynne, Alfonso Blanco, Jan Zivny, Valeria Lima Passos, Barry Kevane, Seán Murphy, Fionnuala Ní Áinle, Martin O'Donnell, Patricia B Maguire
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Abstract

Background: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD.

Objectives: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime.

Methods: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis.

Results: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up.

Conclusion: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.

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利伐沙班联合小剂量阿司匹林可减少心血管疾病患者的促炎症和促血栓形成循环囊泡特征。
背景:尽管使用了阿司匹林进行二级预防,但病情稳定的心血管疾病(CVD)患者发生重大心血管事件(MACE)的长期风险仍然很高。COMPASS 双盲随机临床试验表明,与单用阿司匹林相比,阿司匹林加小剂量利伐沙班(COMPASS 方案)可将 MACE 发生率显著降低 24%。然而,这些潜在的协同/非抗血栓作用的机制仍然难以捉摸。细胞外囊泡(EVs)是调节无数生物/病理过程的重要信使,与心血管疾病有很大关系。我们假设循环中的EV能反映COMPASS疗法的心脏保护特性:我们前瞻性地招募了一批参与 COMPASS 试验的稳定型心血管疾病患者(40 人),这些患者之前被随机分配接受阿司匹林治疗,现在他们又被分配接受了开放标签阿司匹林加利伐沙班的修订治疗方案。在基线(仅服用阿司匹林)和6个月随访时采集血样。通过 NTA 和流式细胞术分析血浆 EV 的浓度、大小和来源。通过超速离心法富集 EVs 进行蛋白质组分析:结果:COMPASS 方案从根本上改变了小EV(结论:观察到的 EV 亚群的变化以及不同的蛋白质表达谱表明,双重疗法改善了潜在的促炎症和促血栓形成状态,这可能与临床相关,有助于理解与这种抗血栓治疗方案相关的卓越心血管疗效的基本机制。
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来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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