Dual Pathway Inhibition with Rivaroxaban and Aspirin Reduces Inflammatory Biomarkers in Atherosclerosis

Abstract

ABSTRACT: Dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) reduces the occurrence of cardiovascular (CV) events; however, the underlying mechanisms explaining these latter CV benefits are not clearly understood. Our explorative observational study aimed to evaluate the effect of dual pathway inhibition on plasma inflammation and coagulation markers among real-world patients with CAD and/or PAD. We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin 100 mg once daily (OD) and rivaroxaban 2.5 mg twice daily (TD). Clinical evaluation and laboratory analyses, including hemoglobin, renal function (creatinine, urea, and cystatin-C), coagulation markers (INR and aPTT), inflammation markers (IL-6, CRP, lipoprotein-associated phospholipase A2, and copeptin), and growth differentiation factor-15 (GDF-15), were conducted at baseline, before starting treatment, and at 4 and 24 weeks after study drug administration. Fifty-four consecutive patients (mean age 66 ± 7 years; male 83%) who completed the 6-month follow-up were included. At 24-week follow-up, a statistically significant reduction in IL-6 serum levels [4.6 (3.5-6.5) vs. 3.4 (2.4-4.3) pg/mL ; P = 0.0001] and fibrinogen [336 (290-390) vs. 310 (275-364) mg/dL; P = 0.04] was shown; moreover, a significant increase in GDF-15 serum level [1309 (974-1961) vs. 1538 (1286-2913) pg/mL; P = 0.002] was observed. Hemoglobin, renal function, and cardiovascular homeostasis biomarkers remain stable over the time. The anti-Xa activity at both [0.005 (0-0.02) vs. 0.2 (0.1-0.34); P < 0.0001) significantly increased. The dual pathway inhibitions with low-dose rivaroxaban and aspirin in patients with CAD and/or PAD were associated with the reduction of inflammation biomarkers.