Anti-inflammatory effect of factor-Xa inhibitors in Japanese patients with atrial fibrillation

Abstract

Activated factor-X (FXa) plays an important role not only in the coagulation cascade, but also in pro-inflammatory responses. However, few data exist regarding the anti-inflammatory effect of FXa inhibitors in clinical practice. The aim of this study was to evaluate the anti-inflammatory and anti-atherosclerotic effects of FXa inhibitors in Japanese patients with non-valvular atrial fibrillation (NVAF). Eighty-three patients with NVAF were treated with FXa inhibitors from March 2013 to March 2015 at our institution. Of these, 55 patients who were not pretreated with warfarin or dabigatran (rivarixaban in 23 patients and apixaban in 32) were included in this study. We measured various inflammatory and coagulation markers at baseline and at 6 months after treatment. Plasma concentrations of pentraxin 3 (PTX3) (from 2.45 ± 1.31 to 1.97 ± 1.00 ng/mL, p = 0.0009) and fibrin and fibrinogen degradation products (FDP) D-dimer (from 1.18 ± 0.70 to 0.74 ± 0.32 μg/mL, p < 0.0001) decreased, while those of TM (from 2.9 ± 0.8 to 3.2 ± 0.9 FU/mL, p = 0.003) increased significantly at 6 months. Interestingly, change of each marker denoted the same tendency in both rivaroxaban and apixaban. In conclusion, the present study suggests that FXa inhibitors have not only an anti-coagulant effect but also anti-inflammatory effects in patients with NVAF. Further large-scale prospective study is necessary to evaluate whether changes in these markers will be associated with a lower risk for future cardiovascular events.

Persistent Systemic Inflammation Is Associated With Bleeding Risk in Atrial Fibrillation Patients

“…In the clinical setting, however, the anti-inflammatory effect of DOAC was still controversial. 9,21 In the present study median hsCRP was significantly reduced (0.03 mg/dL; IQR, 0.02-0.04 mg/dL, P<0.001) 6±3 months after initiation of DOAC therapy. Treatment was not basically changed between pre-and post-DOAC hsCRP assessments, except for initiation of the DOAC.…”

Potential Therapeutic Roles for Direct Factor Xa Inhibitors in Coronavirus Infections

“…Importantly, the anti-inflammatory effects of FXa inhibitors have been demonstrated in human subjects. For example, the anti-inflammatory effects of rivaroxaban and apixaban were recently observed in Japanese patients with atrial fibrillation [64]. The anti-inflammatory effect of apixaban was also recently demonstrated in the acute phase of ischemic stroke patients [65].…”

Inhibition of activated factor X; a new pathway in ameliorating carbon tetrachloride–induced liver fibrosis in rats

“…In the past few years, many researchers postulated a strong relationship between coagulation cascade and several nonhematological pathological conditions. The pathological role of coagulation system has been recognized in different inflammatory diseases . Davalos and Akassoglou reported that fibrinogen is a potent proinflammatory agent.…”

“…Factor Xa was reported to stimulate the production of the proinflammatory and profibrotic mediators by retinal pigment epithelial cells. [29] Interestingly, Katoh et al recently showed that the beneficial effect of factor Xa inhibitors in atrial fibrillation clinically is attributed not only to direct antithrombotic effect but also to their anti‐inflammatory effect.…”