Effects of Rivaroxaban on Biomarkers of Coagulation and Inflammation: A Post Hoc Analysis of the X-VeRT Trial

Abstract

Introduction This X-VeRT (eXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion) substudy evaluated the effects of treatment with rivaroxaban or a vitamin-K antagonist (VKA) on levels of biomarkers of coagulation (D-dimer, thrombin–antithrombin III complex [TAT] and prothrombin fragment [F1.2]) and inflammation (high sensitivity C-reactive protein [hs-CRP] and high-sensitivity interleukin-6 [hs-IL-6]) in patients with atrial fibrillation (AF) who were scheduled for cardioversion and had not received adequate anticoagulation at baseline (defined as, in the 21 days before randomization: no oral anticoagulant; international normalized ratio <2.0 with VKA treatment; or <80% compliance with non-VKA oral anticoagulant treatment). Methods Samples for biomarker analysis were taken at baseline (n = 958) and treatment completion (42 days after cardioversion; n = 918). The influence of clinical characteristics on baseline biomarker levels and the effect of treatment on changes in biomarker levels were evaluated using linear and logistic models. Results Baseline levels of some biomarkers were significantly associated with type of AF (D-dimer and hs-IL-6) and with history of congestive heart failure (hs-CRP, D-dimer, and hs-IL-6). Rivaroxaban and VKA treatments were associated with reductions from baseline in levels of D-dimer (−32.3 and −37.6%, respectively), TAT (−28.0 and −23.1%, respectively), hs-CRP (−12.5 and −17.9%, respectively), and hs-IL-6 (−9.2 and −9.8%, respectively). F1.2 levels were reduced from baseline in patients receiving a VKA (−53.0%) but not in those receiving rivaroxaban (2.7%). Conclusion Anticoagulation with rivaroxaban reduced levels of key inflammation and coagulation biomarkers to a similar extent as VKAs, with the exception of F1.2. Further investigation to confirm the value of these biomarkers in patients with AF is merited.

Potential Therapeutic Roles for Direct Factor Xa Inhibitors in Coronavirus Infections

“…The anti-inflammatory effect of apixaban was also recently demonstrated in the acute phase of ischemic stroke patients [65]. A post hoc analysis of the X-VeRT trial also revealed that rivaroxaban caused a significant reduction in the levels of D-dimer and IL-6 in patients with atrial fibrillation [66]. These results indicate that blocking the activity of FXa may not only be beneficial to prevent the virus-associated coagulopathies but may also dampen the virus-triggered excessive immune response.…”

Interplay between inflammation and thrombosis in cardiovascular pathology

“…In experimental models of myocardial ischaemia–reperfusion injury, the inflammatory response mediated by NF-κB and inflammasome activation was attenuated by inhibition of factor Xa, characterized by the decreased expression of pro-inflammatory mediators 199 . In patients with atrial fibrillation, oral anticoagulation with rivaroxaban or a vitamin K antagonist decreased the levels of IL-6 and C-reactive protein in the plasma 205 . The molecular link for this bidirectional interplay of thrombosis and inflammation might be proteinase-activated receptors (PARs), which self-activate after proteolytic cleavage by serine proteases such as factor X and thrombin 201 .…”

Comparison of Inflammatory Mediators in Patients With Atrial Fibrillation Using Warfarin or Rivaroxaban

“…Taken together, these data demonstrate that patients with AF might benefit from the use of anticoagulants with anti-inflammatory properties. Accordingly, a recent study has demonstrated that the treatment with rivaroxaban (43-98 days, depending on cardioconversion) was associated with reductions in both CRP and IL-6 in comparison with baseline levels (21). However, the evidence is still scarce, and it points out the need for trials seeking to investigate the levels of inflammatory mediators in patients with AF under different anticoagulant therapies.…”