For patients with type 2 diabetes (T2D), rivaroxaban therapy improved endothelial function, but increased bleeding risk. These findings were published in Diabetologia.
A multicenter, prospective, randomized, open-label clinical trial funded by Bayer Vital AG, makers of Xarelto ® (the brand name of rivaroxaban) recruited patients (N=179) with T2D who had subclinical inflammation and endothelial dysfunction. Patients 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. Vascular and endothelial function were assessed at baseline and trial conclusion.
At baseline, the rivaroxaban and aspirin control cohorts were aged mean 64.2±7.4 and 64.7±6.8 years, the male:female ratio was 38:51 and 46:44, body mass index (BMI) was 33.2±5.3 and 33.4±5.1 kg/m2, and glycated hemoglobin (HbA1c) was 6.9%±0.8% and 6.9%±1%, respectively.
In general, 20 weeks of rivaroxaban improved coagulation variables. For example, the maximal forearm blood flow (FBF) compared with baseline was increased by 3.6±4.7 ml/100 ml for rivaroxaban and 1.0±5.2 ml/100 ml for aspirin (P =.004).
Compared with baseline, recipients of rivaroxaban had improved FBF area under the curve, soluble P-selectin, and platelet-derived microparticles (all P <.02). For the aspirin recipients, there were improvements to high-sensitivity C-reactive protein and platelet-derived microparticles (both P <.02).
In the complete context of vascular and endothelial health, markers for endothelial function tended to favor rivaroxaban therapy and markers of inflammation tended to favor aspirin therapy.
There was 1 clinically relevant non-major bleeding event and 2 minor bleeding events among the aspirin recipients. For the rivaroxaban treatment group, there was 1 major bleeding event, 11 clinically relevant non-major bleeding events, and 8 minor bleeding events, indicating there was higher risk for bleeding with rivaroxaban treatment (P <.01).
This study was limited by the differing delivery methods (once daily for aspirin vs twice daily for rivaroxaban) and the fact there was no combined rivaroxaban/aspirin treatment arm.
The study authors concluded rivaroxaban improved endothelial function among patients with T2D and subclinical inflammation, but also increased the risk of bleeding “Further trials of longer duration are needed to clarify whether inhibition of factor Xa can reduce cardiovascular outcomes with an acceptable risk of bleeding in an early stage of atherosclerosis,” they said.
Disclosure: Multiple authors declared affiliations with industry, and the study was supported by a research grant from Bayer Vital AG, makers of Xarelto® (the brand name of rivaroxaban). Please refer to the original article for a full list of disclosures.
Pistrosch F, Matschke JB, Schipp D, et al. Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers. Diabetologia. Published online September 8, 2021. doi:10.1007/s00125-021-05562-9