Trained Immunity by Dual-pathway Inhibition in Coronary Artery Disease

Summary

Coronary artery disease (CAD) is a manifestation of systemic atherosclerosis for which single antiplatelet therapy (SAPT) is indicated 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 exact mechanisms underlying the benefits of DPI, are not completely understood. CAD is characterised by a state of chronic low-grade inflammation, where monocytes from CAD patients have a higher immune responsiveness to ex vivo stimulation with lipopolysaccharide (LPS) compared to healthy matched controls. Surprisingly, the investigators 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from ASA monotherapy to DPI of ASA combined with rivaroxaban inpatients with peripheral arterial disease (n=11; unpublished).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 systemic inflammation, as determined by Olink proteomics analysis. These findings suggest that factor Xa inhibitors can enhance immune cell responsiveness despite being clinically beneficial to CAD. The exact mechanisms contributing to the observed increased immune responsiveness remain unexplored.

Timeline

Start

2022-03-01

Primary completion

2022-04-15

Completion

2022-07-01

Publications

• Groh LA, Willems LH, Fintelman P, Reijnen MMPJ, El Messaoudi S, Warle MC. Dual-Pathway Inhibition with Rivaroxaban and Low-Dose Aspirin Does Not Alter Immune Cell Responsiveness and Distribution in Patients with Coronary Artery Disease. Cardiol Ther. 2024 Mar;13(1):233-242. doi: 10.1007/s40119-023-00342-5. Epub 2023 Dec 6.

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