Diabetes Res Clin Pract. 2025 May 9:112244. doi: 10.1016/j.diabres.2025.112244. Online ahead of print.
ABSTRACT
AIMS: A very-low-dose regimen of the anti-factor Xa rivaroxaban combined with low-dose aspirin reduces vascular events more than aspirin alone in atherosclerotic patients, including those with type 2 diabetes (T2DM). Given the high platelet activation in T2DM patients, we investigated whether this combination reduces platelet activation versus aspirin alone and the possible mechanisms.
METHODS: Seventy-5 patients (12 females, aged 69[65-72]), with stable atherothrombotic disease, on low-dose aspirin, participated in a randomized, cross-over, open-label, study with two arms: 4-week aspirin (100 mg once-daily) followed by 4-week aspirin plus rivaroxaban (2.5 mg twice-daily); 4-week aspirin plus rivaroxaban followed by 4-week aspirin. We investigated: in vivo platelet activation by urinary thromboxane A metabolite (TXM), thrombin generation (TG), endothelial function by urinary prostacyclin and plasma nitric oxide metabolites, lipid oxidation by urinary isoprostane, inflammation, coagulation biomarkers.
RESULTS: No carryover effects were observed. Rivaroxaban plus aspirin significantly reduced urinary TXM and isoprostane versus aspirin alone (20 %[95 %CI:5-31 %] and 19 %[12-26 %], respectively, n = 73, p < 0.01). At rivaroxaban's maximal concentration, TG velocity index and peak were reduced by 44 %[37-52 %] and 81 %[75-87 %], respectively, versus aspirin alone. Inflammation and endothelial biomarkers were unchanged.
CONCLUSIONS: Very-low-dose rivaroxaban and low-dose aspirin in T2DM patients significantly inhibit in vivo platelet function, TG and isoprostane formation. EudraCT Number: 2019-000610-10.
PMID:40349848 | DOI:10.1016/j.diabres.2025.112244