Healthy subjects (N = 51) were enrolled in a randomized, crossover (rivaroxaban 5, 10 or 20 mg with or without ASA), and parallel-group (compared with ASA plus clopidogrel) study. Thrombi formed on pig aorta strips were measured after a 5-minute perfusion at low and high shear rates with blood from the subjects by measuring D-dimer concentration (for fibrin deposition) and P-selectin content (for platelet deposition).
ASA alone had no impact on thrombus D-dimer levels, whereas rivaroxaban alone at peak concentrations decreased D-dimer levels by 9 % , 84 % and 65 % at low shear rate and 37 % , 73 % and 74 % at high shear rate after doses of 5, 10 and 20 mg, respectively. Steady-state ASA plus rivaroxaban 5 mg caused a greater reduction in D-dimer levels (63 % ) than monotherapy at low shear rate. Co-administration of ASA with clopidogrel was associated with a 30 % decrease in D-dimer levels at low shear rate and a 14 % decrease at high shear rate. No conclusive effect on P-selectin content was observed across the treatment groups.
Rivaroxaban dose-dependently inhibited ex vivo thrombus formation under low and high shear rates. Co-administration of ASA had an additional effect on the antithrombotic action of low-dose rivaroxaban.