714 PLEIOTROPIC EFFECTS OF ANTICOAGULANT THERAPIES: IS THERE A DIFFERENCE BETWEEN AVK AND DOAC?
Authors: Alfano Francesco , Maria Gori Anna , Cesari Francesca , Salvadori Emilia , Giusti Betti , Lotti Elena , Poggesi Anna , Marcucci Rossella 
Published: December 2022

Abstract

Background
Atrial fibrillation (AF) is the most common supraventricular arrhythmia. Emerging evidence suggests a significant role of inflammation in the pathogenesis and in the maintenance of AF. We hypothesize a different role of anticoagulant therapy (AVK vs. DOACs) in reducing the levels of inflammatory biomarkers in AF.

Methods
The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with atrial fibrillation, aged 65 years or older, and with no contraindications to undergo magnetic resonance imaging. Recruited patients are evaluated by means of a comprehensive protocol, with clinical and circulating biomarkers assessment. One of the main outcomes is the evaluation of the grade of inflammation in patients treated with AVK vs. DOACs. In order to evaluate the grade of inflammation, we calculated the ratios between pro- and anti-inflammatory cytokines (IL6/IL4, IL6/IL10, TNF-alpha/IL4, TNF-alpha/IL10). The pro-/anti-inflammatory ratios were divided into tertiles and were used to calculate a score of inflammation. Patients with ratios in the third tertile were assigned as patients with an elevated grade of inflammation not balanced by anti-inflammatory cytokines; patients with ratios in the other tertiles were assigned as patients with a low level of inflammation. Starting from September 2017, 191 patients (mean age 78.1±6.7, range 65-97; 65.3% males) were enrolled. 56 patients (29.3%) were on vitamin K antagonists, and 135 (70.7%) were on direct oral anticoagulants.

Results
Patients treated with DOACS had higher ratio values than patients treated with AVK [IL6/IL4: 0.15 (0.07-0.35) vs 0.05 (0.03-0.25), p=0.001; IL6/IL10: 0.70 (0.28-5.49) vs 0.54 (0.18-1.42), p=0.090; TNF-alpha/IL4: 0.16 (0.12-0.31) vs 0.13 (0.08-0.31), p= 0.055; TNF-apha/IL10: 0.97 (0.25-5.23) vs 0.75 (0.51-2.62), p=0.105]. According to pro-anti-inflammatory ratio tertiles, 28/135 DOAC patients (20.7%) had an elevated grade of inflammation not balanced by anti-inflammatory cytokines, whereas in AVK group only 5.4% (3/53) were classified as patients with high levels of inflammation (p=0.009). At multivariate logistic regression analysis, adjusted for age, sex, CHA2DS2-VASc, HAS-BLED, AVK treatment resulted an independent and protective predictor for having a high grade of inflammation not balanced by anti-inflammatory cytokine levels [OR=0.27 (0.08-0.97), p=0.045].

Conclusions
These result from Strat-AF study may be an essential step towards the exploration of the role and the contribute of anticoagulant therapy in reducing inflammation-related biomarkers in AF patients. Inflammation has also been associated with endothelial dysfunction, coagulation cascade activation and thrombogenesis. Thus, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications. These results might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting