# Rivaroxaban versus warfarin: differential effects on oxidative stress and fibrinolytic markers in atrial fibrillation

**Authors:** Helton Jose Reis, Luana Bernardes Xavier Costa, Gabriela Lopes Martins, Rita Carolina Figueiredo Duarte, Luma Clara Martins Costa, Estêvão Lanna Figueiredo, Francisco Rezende Silveira, Nathália Greco Coelho, Maria das Graças Carvalho, Luciene Bruno Vieira, Edna Afonso Reis, Karina Braga Gomes, Cláudia Natália Ferreira

PMC · DOI: 10.3389/fphar.2026.1685101 · Frontiers in Pharmacology · 2026-01-19

## TL;DR

This study compares rivaroxaban and warfarin in atrial fibrillation patients, finding that rivaroxaban may improve cellular metabolism and reduce clotting-related proteins more effectively.

## Contribution

The study reveals novel pleiotropic effects of rivaroxaban on oxidative stress and fibrinolytic markers in AF patients.

## Key findings

- Rivaroxaban showed higher MTT absorbance, indicating better cellular metabolic activity.
- Rivaroxaban was associated with significantly lower TAFI levels compared to warfarin.
- The drug may enhance antioxidant mechanisms and suppress antifibrinolytic activity in AF patients.

## Abstract

Atrial fibrillation (AF) is a cardiac arrhythmia characterized by disorganized atrial electrical activity, resulting in ineffective mechanical contraction and a heightened propensity for intra-atrial thrombus formation. The underlying pathophysiology is multifactorial, involving a complex interplay of pro-fibrotic, inflammatory, and pro-thrombotic pathways, notably oxidative stress and dysregulation of the fibrinolytic system. Given that these mechanisms remain incompletely elucidated, this study sought to investigate the association between biomarkers of oxidative stress and antifibrinolytic activity in AF patients treated with the oral anticoagulants warfarin or rivaroxaban, in comparison to a healthy control cohort.

A total of 85 AF patients—38 on rivaroxaban and 47 on warfarin—were enrolled alongside 62 matched healthy controls. Cellular metabolic activity was assessed via MTT [3-(4,5-Dimethylthiazol-2γl)-2,5-Diphenyl Tetrazoline Bromide] assay measured by spectrophotometry. Serum concentrations of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation), plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor (TAFI) were quantified using enzyme-linked immunosorbent assay (ELISA).

The rivaroxaban group exhibited significantly greater MTT absorbance, indicative of enhanced cellular metabolic activity, and significantly lower circulating TAFI levels compared to the warfarin group.

These results suggest that in patients with AF, rivaroxaban may provide pleiotropic benefits beyond anticoagulation, potentially by augmenting cellular antioxidant mechanisms and suppressing antifibrinolytic activity.

## Linked entities

- **Proteins:** SERPINE1 (serpin family E member 1), CPB2 (carboxypeptidase B2)
- **Chemicals:** rivaroxaban (PubChem CID 6433119), warfarin (PubChem CID 54678486)
- **Diseases:** atrial fibrillation (MONDO:0004981)

## Full-text entities

- **Genes:** SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, CPB2 (carboxypeptidase B2) [NCBI Gene 1361] {aka CPU, PCPB, TAFI}
- **Diseases:** atrial thrombus (MESH:D013927), cardiac arrhythmia (MESH:D001145), inflammatory (MESH:D007249), AF (MESH:D001281)
- **Chemicals:** TBARS (MESH:D017392), 3-(4,5-Dimethylthiazol-2gammal)-2,5-Diphenyl Tetrazoline Bromide (-), Rivaroxaban (MESH:D000069552), lipid (MESH:D008055), warfarin (MESH:D014859), MTT (MESH:C070243)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12862254/full.md

## References

57 references — full list in the complete paper: https://tomesphere.com/paper/PMC12862254/full.md

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Source: https://tomesphere.com/paper/PMC12862254