Trained Immunity by Dual-pathway Inhibition (Low-dose Rivaroxaban and Acetylsalicylic Acid) in Coronary Artery Disease'
Overview
- Phase
- Phase 4
- Intervention
- Rivaroxaban 2.5 Mg Oral Tablet
- Conditions
- Coronary Artery Disease
- Sponsor
- Radboud University Medical Center
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Whole blood immune responsiveness
- Last Updated
- 4 years ago
Overview
Brief 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from ASA monotherapy to DPI of ASA combined with rivaroxaban inpatients with peripheral arterial disease (n=11; unpublished).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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- •stable CAD
- •with an indication for single antiplatelet therapy according to international (ESC) guidelines,
- •high cardiovascular risk based on a SMART risk score \[9\] of at least 20% and/or the judgement of the cardiologist
- •at least 1 year after myocardial infarction or multivessel CAD
- •\>16 years old
- •Written informed consent
Exclusion Criteria
- •A potential subject who meets any of the following criteria will be excluded from participation in this study:
- •Use of more intensive antithrombotic treatment (dual antiplatelet therapy, DPI, direct oral anticoagulants, vitamin k antagonists)
- •Use of immunosuppressant and/or anti-inflammatory therapy, including glucocorticoids, cytostatics, antibodies, immunophilins, interferons, Tumor Necrosis Factor (TNF) binding proteins, mycophenolate and interleukin antagonists
- •Contra-indication to rivaroxaban
- •Hypersensitivity to rivaroxaban
- •at significant risk for major bleeding
- •current gastrointestinal ulceration
- •presence of malignant neoplasms, with the exception of non-melanoma skin cancer
- •recent (\<2 months) brain or spinal injury
- •recent (\<3 months) brain or spinal surgery
Arms & Interventions
Stable coronary artery disease
Patients with stable coronary artery disease with an indication for single antiplatelet therapy according to international (ESC) guidelines, with a high cardiovascular risk.
Intervention: Rivaroxaban 2.5 Mg Oral Tablet
Outcomes
Primary Outcomes
Whole blood immune responsiveness
Time Frame: 12 weeks
Change in whole blood immune responsiveness to lipopolysaccharide stimulation when switching from acetylsalicylic acid to dual pathway inhibition (acetylsalicylic acid and low-dose rivaroxaban).
Secondary Outcomes
- White blood cell count and distribution(3 months)
- Enrichment of epigenetic marks on genes(3 months)
- Monocyte immune responsiveness(3 months)