Factor Xa inhibition by rivaroxaban in the trough steady state can significantly reduce thrombin generation.

The aim of the present study was to demonstrate evidence of reduced thrombin generation at the trough plasma rivaroxaban concentration. A single-centre, prospective, nonrandomized, drug-intervention, self-controlled study was conducted in 51 anticoagulation therapy-naïve patients with nonvalvular atrial fibrillation. Plasma rivaroxaban concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and the anti-factor Xa chromogenic assay. Partial thrombin time (PT), protein C activity, and protein S antigen, prothrombin fragment 1 + 2 (F1 + 2), D-dimer, thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI) levels were also measured at the trough steady state after 4 weeks of rivaroxaban treatment and compared with baseline. Plasma concentrations obtained by the LC-MS/MS and anti-Xa assays were correlated (r = 0.841, P < 0.001). The mean concentration of rivaroxaban at the trough steady state was 23.6 ng ml-1 , at which F1 + 2, TAT and D-dimer had decreased from the baseline values (P < 0.0001, P = 0.029 and P < 0.005, respectively). PT was prolonged (+0.59 s, P < 0.0001). TFPI increased from baseline to the trough steady state in the first to third quartile groups (+0.79 pg ml-1 , P = 0.048). By contrast, PAI-1, protein C activity, protein S antigen and TM remained within the normal range at the trough steady state. Residual plasma rivaroxaban at the trough steady state may explain the antithrombin effect of rivaroxaban in patients with nonvalvular atrial fibrillation.

Horinaka S ，Sugawara R ，Yonezawa Y ，Ishimitsu T ... -  《-》

Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation.

Al-Aieshy F ，Malmström RE ，Antovic J ，Pohanka A ，Rönquist-Nii Y ，Berndtsson M ，Al-Khalili F ，Skeppholm M ... -  《-》

Intra- and inter- individual rivaroxaban concentrations and potential bleeding risk in patients with atrial fibrillation.

Miklič M ，Mavri A ，Vene N ，Söderblom L ，Božič-Mijovski M ，Pohanka A ，Antovic J ，Malmström RE ... -  《-》

[Evaluation of oral anticoagulation with rivaroxaban, in patients with new onset non valvular atrial fibrillation].

Neira V ，Corbalán R ，Pereira J ，Panes O ，Garayar B ，Aizman A ，Llevaneras S ，Villarroel L ... -  《-》

Assessment of trough rivaroxaban concentrations on markers of coagulation activation in nonvalvular atrial fibrillation population.

Kitagawa F ，Ishii J ，Hiramitsu S ，Takahashi H ，Okuyama R ，Kawai H ，Muramatsu T ，Harada M ，Motoyama S ，Naruse H ，Matsui S ，Sarai M ，Hayashi M ，Watanabe E ，Izawa H ，Ozaki Y ... -  《-》