Comparison of anti-inflammatory effects of rivaroxaban vs. dabigatran in patients with non-valvular atrial fibrillation (RIVAL-AF study): multicenter randomized study

Heart Vessels. 2019 Jun;34(6):1002-1013. doi: 10.1007/s00380-018-01324-7. Epub 2019 Jan 1.

Abstract

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.

Keywords: Atrial fibrillation; Bleeding; Direct oral anticoagulation; Inflammation; Thrombomodulin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Dabigatran / adverse effects
  • Dabigatran / therapeutic use*
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Regression Analysis
  • Rivaroxaban / adverse effects
  • Rivaroxaban / therapeutic use*
  • Severity of Illness Index
  • Stroke / etiology
  • Stroke / prevention & control*

Substances

  • Anticoagulants
  • Rivaroxaban
  • Dabigatran