Abstract 2991: Effect of Rivaroxaban on Biomarkers of Hypercoagulability in Patients With Chronic Heart Failure
Background: Markers of hypercoagulability (D-dimer (DD), prothrombin fragment 1.2 (F1.2), and thrombin-antithrombin III complex (TAT)) are increased in chronic heart failure (HF) and associated with increased mortality. An increased incidence of venous and arterial thrombo-embolic events is noted in HF. The objective of this study was to examine the effect of rivaroxaban - an oral, highly selective, direct Factor Xa inhibitor - on the circulating concentration of DD, F1.2 and TAT in patients with NYHA class III/IV chronic HF.
Methods: 18 patients (mean age 61 years, 28% women, mean LVEF 21%) were randomized 2:1 to receive either rivaroxaban (n=12; 10mg qd) or placebo (n=6) for 6 days. Blood samples were obtained prior to administration of blinded study medication and 24 hours after the last dose. The primary end point was the mean difference in change from baseline between the two treatment groups.
Results: Rivaroxaban appeared safe and was well tolerated. In patients receiving rivaroxaban, the mean concentration of F1.2 decreased by 2.7ng/ml (±0.9) over 7 days, compared to an increase of 11.6ng/ml (±4.2) in subjects receiving placebo, an absolute difference of 14.3ng/ml (±3.3), P=0.0009. A trend in attenuation was seen for DD and TAT (Fig⇓).
Conclusions: In patients with moderately severe chronic HF, in-vivo markers of coagulation appear to increase over time. Rivaroxaban reversed this trend for F1.2 with some evidence of attenuation for DD and TAT. Rivaroxaban is being studied in large clinical trials in patients who frequently have concomitant HF. These results support further study of rivaroxaban for the prevention of thromboembolism in HF.