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.
- MeSH
- Aspirin * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- extracelulární vezikuly * metabolismus účinky léků MeSH
- inhibitory agregace trombocytů * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- inhibitory faktoru Xa * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kardiovaskulární nemoci * krev prevence a kontrola farmakoterapie MeSH
- kombinovaná farmakoterapie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu krev MeSH
- prospektivní studie MeSH
- proteomika metody MeSH
- rivaroxaban * aplikace a dávkování MeSH
- senioři MeSH
- trombóza krev prevence a kontrola farmakoterapie MeSH
- výsledek terapie MeSH
- zánět krev 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
