Trained Immunity by Dual-pathway Inhibition in Coronary Artery Disease
Status:
Not yet recruiting
Trial end date:
2022-07-31
Target enrollment:
Participant gender:
Summary
Coronary artery disease (CAD) is a manifestation of systemic atherosclerosis for which single
antiplatelet therapy (SAPT) isindicated if patients are stable. Recently dual pathway
inhibition (DPI) by combining a low-dose factor Xa inhibitor (rivaroxaban2.5mg twice daily)
with a single platelet inhibitor (ASA) has been demonstrated to be beneficial in treating
CAD. The exactmechanisms underlying the benefits of DPI, are not completely understood. CAD
is characterised by a state of chronic low-gradeinflammation, where monocytes from CAD
patients have a higher immune responsiveness to ex vivo stimulation withlipopolysaccharide
(LPS) compared to healthy matched controls. Surprisingly, we have recently observed an
elevation in ex vivo immune responsiveness to LPS stimulation when switching from ASA
monotherapy to DPI of ASA combined with rivaroxaban inpatients with peripheral arterial
disease (n=11; unpublished). Remarkably this was associated with no changes in
systemicinflammation, as determined by Olink proteomics analysis. These findings suggest that
factor Xa inhibitors can enhance immunecell responsiveness despite being clinically
beneficial to CAD. The exact mechanisms contributing to the observed increasedimmune
responsiveness remain unexplored.