Rivaroxaban Enhances Endothelial Function in Patients with Type 2 Diabetes: Study

Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Previous studies demonstrated that the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin significantly reduces major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. However, the effects on endothelial function in individuals receiving direct factor Xa inhibition have never been measured before. Therefore, Dr Frank Pistrosch and his team conducted a study to determine whether treatment with the direct factor Xa inhibitor rivaroxaban in type 2 diabetic patients at high cardiovascular risk could influence endothelial function, microvascular blood flow, arterial stiffness, serum biomarkers of inflammation and platelet activation.

It was a multicenter, prospective, randomized, open-label clinical trial funded by Bayer Vital AG, makers of Xarelto ®. The researchers included a total of 179 patients with T2D who had subclinical inflammation and endothelial dysfunction. They were randomized to receive 5 mg twice daily of the direct factor Xa inhibitor rivaroxaban (n=89) or 100 mg once daily aspirin (n=90) for 20 weeks. The researchers evaluated endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. They further investigated the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro.

Key findings of the study were:

• Upon analysis for 20 weeks, the researchers found that rivaroxaban treatment significantly improved post-ischemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level when compared with aspirin.
• However, they found no significant differences in arterial stiffness or further biomarkers.
• They noted that neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets.
• They also noted a significant increase in the number of PMPs with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1).
• They found that PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin.
• However, they observed a high number of bleeding events with rivaroxaban.

The authors concluded, "Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding."

For further information:

https://doi.org/10.1007/s00125-021-05562-9