Activated factor XI is associated with increased factor VIIa – Antithrombin complexes in stable coronary artery disease: Impact on cardiovascular outcomes.

Background: Coronary artery disease (CAD) is associated with a prothrombotic tendency including increased factor (F) VIIa‐antithrombin (FVIIa‐AT) complexes, a measure of tissue factor (TF) exposure, and activated FXI (FXIa). We investigated whether increased FVIIa–AT complexes are associated with FXIa and active TF and if major adverse clinical outcomes are predicted by the complexes in CAD. Methods: In 120 CAD patients, we assessed FVIIa–AT complex concentrations and the presence of circulating FXIa and active TF. Levels of 8‐iso‐prostaglandin F2α (8‐iso‐PGF2α), interleukin‐6, high‐sensitivity C reactive protein, prothrombin fragment 1 + 2, and free Tissue Factor Pathway Inhibitor were determined. Myocardial infarction (MI), ischemic stroke, systemic thromboembolism (SE), and cardiovascular (CV) death were recorded separately and as a composite endpoint, during follow‐up. Results: FVIIa–AT complexes were positively associated with current smoking and multivessel CAD. Elevated FVIIa–AT complexes characterized patients with circulating FXIa and/or active TF in association with increased plasma isoprostanes but not with thrombin generation or inflammatory markers. During a median follow‐up of 106 months (interquartile range 95–119), high baseline levels of FVIIa–AT complexes predicted ischemic stroke/SE (HR 4.61 [95% CI 1.48–18.42]) and a composite endpoint of MI, stroke/SE, and CV death (HR 7.47 [95% CI 2.81–19.87]). Conclusions: This study is the first to show that high FVIIa–AT complexes characterize advanced CAD patients with detectable FXIa and active TF, which is, in part, driven by oxidative stress. High FVIIa–AT complexes were associated with the risk of ischemic stroke/SE during long‐term follow‐up, highlighting the need for effective antithrombotic agents in CAD. [ABSTRACT FROM AUTHOR]