Rivaroxaban, in combination with low-dose aspirin, is associated with a reduction in proinflammatory and prothrombotic circulating vesicle signatures in patients with cardiovascular disease
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, randomizované kontrolované studie
PubMed
39413927
DOI
10.1016/j.jtha.2024.09.030
PII: S1538-7836(24)00579-8
Knihovny.cz E-zdroje
- Klíčová slova
- aspirin, cardiovascular disease, extracellular vesicles, proteomics, rivaroxaban,
- MeSH
- Aspirin * aplikace a dávkování škodlivé účinky MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- dvojitá slepá metoda MeSH
- extracelulární vezikuly * metabolismus účinky léků MeSH
- fibrinolytika * aplikace a dávkování škodlivé účinky MeSH
- inhibitory agregace trombocytů * aplikace a dávkování škodlivé účinky MeSH
- inhibitory faktoru Xa * aplikace a dávkování škodlivé účinky MeSH
- kardiovaskulární nemoci * krev farmakoterapie diagnóza MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu * krev MeSH
- prospektivní studie MeSH
- proteomika MeSH
- rivaroxaban * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- trombóza * krev prevence a kontrola MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- Aspirin * MeSH
- biologické markery MeSH
- fibrinolytika * MeSH
- inhibitory agregace trombocytů * MeSH
- inhibitory faktoru Xa * MeSH
- mediátory zánětu * MeSH
- rivaroxaban * MeSH
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.
Flow Cytometry Core Conway Institute University College Dublin Dublin Ireland
Mass Spectrometry Core Systems Biology Ireland University College Dublin Dublin Ireland
School of Pharmacy and Biomolecular Science Royal College of Surgeons in Ireland Dublin Ireland
UCD Conway SPHERE Research Group Conway Institute University College Dublin Dublin Ireland
Citace poskytuje Crossref.org
