Abstract 5020: Effect of Rivaroxaban on Markers of Coagulation in Patients With Acute Coronary Syndromes: An ATLAS ACS-TIMI 46 Substudy
Background: Prothrombin fragments 1 and 2 (F1.2) and D-dimer (DD) are sensitive circulating markers of thrombin generation and fibrinolysis, respectively. Elevated concentrations of F1.2 and DD in ACS patients have been associated with adverse outcomes.
Methods: In ATLAS ACS-TIMI 46, patients were randomized to placebo or the factor Xa inhibitor rivaroxaban (5–20 mg) twice daily (BID) or the same total daily dose once daily (QD). Blood samples were obtained at baseline, 8–24 hrs, and 180 days after drug administration.
Results: 1,006 subjects were included to date in this substudy. At baseline, F1.2 and DD levels were similar in the placebo, rivaroxaban BID, and rivaroxaban QD groups (F1.2: 241, 251, 259 pMol/L; DD: 0.69, 0.79, 0.76 μg/ml). Compared with placebo, rivaroxaban was associated with a significant reduction in F1.2 levels 8–24 hrs after administration in both the BID (240 vs 209 pMol/L, P<0.01) and QD (240 vs 177 pMol/L, P<0.001) groups. DD at baseline vs 8 –24 hrs was significantly increased in placebo patients (0.69 vs 0.75 μg/ml, P<0.05), but unchanged in patients receiving rivaroxaban. By day 180, F1.2 and DD were reduced in placebo patients, presumably because the previous thrombotic state had dissipated; however, patients receiving rivaroxaban continued to have even lower concentrations of both markers of coagulation (Figure⇓).
Conclusions: In patients with ACS, rivaroxaban is associated with a significant, early reduction in F1.2 that persists throughout 180 days of treatment, as well as a reduction in DD evident at 180 days. These findings may explain, in part, the mechanism by which rivaroxaban reduces major cardiovascular events in patients following an ACS.