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. 2025 Jul 30;13(8):1850.
doi: 10.3390/biomedicines13081850.

Pleiotropic Effects of Oral Anticoagulant Therapy: Is There a Difference Between VKAs and DOACs?

Francesco Alfano  1   2 , Anna Maria Gori  1   2 , Martina Berteotti  1   2 , Angela Rogolino  1   2 , Francesca Cesari  1   2 , Emilia Salvadori  3 , Benedetta Formelli  4   5 , Francesca Pescini  4   5 , Carmen Barbato  4 , Betti Giusti  1   2 , Anna Poggesi  4   5 , Rossella Marcucci  1   2
Affiliations

Pleiotropic Effects of Oral Anticoagulant Therapy: Is There a Difference Between VKAs and DOACs?

Francesco Alfano et al. Biomedicines. .

Abstract

Background: Atrial fibrillation (AF) is one of the most common heart rhythm disorders encountered in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF, but certain questions still remain unanswered, in particular whether AF-related inflammation is a cause or a consequence of the arrhythmia, and whether inflammation reflects underlying disease or AF itself. At the current state of the art, scientific evidence on the role of oral anticoagulants (OAC) in modulating pro-inflammatory cytokines implicated in the pathogenesis of AF remains scarce. The aim of our study was to evaluate, in a population of AF patients undergoing OAC, the different roles of anticoagulant therapy [Vitamin K antagonists (VKAs) and direct oral anti-coagulants (DOACs)] in modulating the levels of inflammatory biomarkers in AF. Methods: The Strat-AF study is an observational, prospective, single center, hospital-based study enrolling elderly patients with AF. Results refer to 170 subjects with complete clinical and biohumoral assessment. Results: At multivariate logistic regression analysis, adjusted for several covariates, VKA treatment was an independent protective predictor for having a high grade of inflammation not balanced by anti-inflammatory cytokine levels [OR = 0.26 (0.10-0.69), p = 0.007]. Conclusions: These results from the Strat-AF study are "generators of hypotheses" and provide preliminary evidence for the differential effects of VKAs and DOACs on inflammatory biomarkers (e.g., IL-6, TNF-α) in AF patients. These findings suggest that inflammatory biomarkers could enhance stroke risk prediction models, potentially improving a tailored AF management.

Keywords: atrial fibrillation; biomarkers; direct oral anticoagulants; extracellular matrix; hemostasis; hypofibrinolysis; inflammation; oral anticoagulant therapy; vitamin K antagonist.

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Conflict of interest statement

The authors declare no conflicts of interest.

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