Effects of low-dose rivaroxaban combined with low-dose aspirin versus low-dose aspirin alone on in vivo platelet activation, endothelial function and inflammation in type 2 diabetes patients with stable atherosclerotic disease: the RivAsa randomized, crossover study.

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 A2 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.