OC 16.5 - Rivaroxaban in Combination with Low-Dose Aspirin Is Associated With A Reduction in Pro-Inflammatory and Pro-Thrombotic Circulating Vesicle Signatures in Patients With Cardiovascular Disease

Sunday, June 25, 2023

11:45 – 12:00 ET

Room: 510

Session Available As: On-Demand

Presenting Author(s)

Luisa Weiss, BSc, MSc, PhD

Post-doctoral Scientist
School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland

Co-Author(s)

PS

Paulina Szklanna

Post-doctoral Scientist
School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland
Sarah Kelliher, MB (she/her/hers)

Clinical Research Fellow
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland, Dublin, Ireland
KW

Kieran Wynne

Mass spectrometry technician
Systems Biology Ireland, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland
AB

Alfonso Blanco

Flow Cytometry Technician
Conway Institute Flow Cytometry Core Facility, University College Dublin, Ireland
Dublin, Dublin, Ireland
AO

Aideen O'Doherty

Clinical Trial Manager
National University of Ireland Galway, Galway, Ireland
Galway, Galway, Ireland
Barry Kevane, MB PhD

Consultant Haematologist
Mater Misericordiae University Hospital & University College Dublin
Dublin, Dublin, Ireland
JZ

Jan Zivny

Associate Professor
Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
Prague, Hlavni mesto Praha, Czech Republic
SM

Séan Murphy

Consultant Physician in Acute Stroke Medicine
Department for Stroke Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
Dublin, Dublin, Ireland
MO

Martin O'Donnell

Professor
National University of Ireland Galway, Galway, Ireland
Galway, Galway, Ireland
FN

Fionnuala Ní Áinle

Consultant Haematologist
Department for Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Dublin, Dublin, Ireland
Patricia B. Maguire, PhD

Full Professor
School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland

Background: Despite secondary prevention with aspirin (ASA), patients with stable cardiovascular disease (CVD) remain at heightened long-term risk of major cardiovascular events (MACE). The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) double-blind randomized clinical trial, including nearly 28,000 CVD patients, demonstrated that aspirin combined with low-dose Rivaroxaban (R) significantly decreased the incidence of MACE by 24% and cardiovascular mortality by 18% compared with ASA alone. However the underlying molecular mechanisms remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. We hypothesised that circulating EV profiles reflect the cardioprotective properties of adding R to ASA.

Aims: To characterize changes in plasma EV size, concentration, cellular origin and protein contents induced by ASA+R

Methods: A cohort of stable CVD patients (n=40) who participated in the COMPASS trial (NCT01776424) and were previously randomised to receive ASA, were prospectively recruited following informed written consent and assigned a revised regimen of open-label ASA+R. Blood samples were obtained at baseline (ASA) and 6-months follow-up (ASA+R). Plasma EV concentration, size and origin were determined by single-vesicle analysis. Protein cargoes were analysed by mass spectrometry.

Results: ASA+R fundamentally altered small ( < 200nm) and large (200-1000nm) EV concentration and size, compared to ASA alone. Crucially, levels of platelet-derived, tissue-factor positive and myeloperoxidase-positive EVs significantly decreased at follow-up, potentially contributing to the reduced incidence of thrombotic events associated with adding R to ASA. Comparative proteomic characterisation further revealed a significant decrease in highly pro-inflammatory protein expression at follow-up.

Conclusion(s): The alterations in EV subpopulations, together with differential protein expression profiles, suggest amelioration of an underlying pro-inflammatory and pro-thrombotic state when low-dose R is added to ASA in patients with CVD, which may be of clinical relevance towards understanding the fundamental mechanism underlying the previously reported superior cardiovascular outcomes associated with this antithrombotic regimen.

Learning Objectives:

Understand the potential contribution of extracellular vesicles in the etiology of cardiovascular disease
Understand the aims of the post-marketing phase of the COMPASS trial
Value the use of translational research to decipher potentially relevant molecular signals underlying the combination of anti-platelet and anticoagulation therapy