Pleiotropic properties of direct oral anticoagulants — new therapeutic horizons

Direct oral anticoagulants (DOACs), including factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) and the direct thrombin inhibitor dabigatran, are widely used for the prevention and treatment of thrombotic complications, particularly in patients undergoing major joint replacement, with atrial fibrillation (AF), as well as part of dual antithrombotic therapy (anticoagulant + antiplatelet) in patients after acute coronary syndrome and percutaneous coronary interventions, especially in the context of concomitant AF and an increased risk of systemic embolism. In recent years, there has been growing interest in studying the pleiotropic effects of DOACs that extend beyond their primary anticoagulant action on the hemostatic system. Accumulating experimental and clinical data suggest that these agents possess additional pharmacological properties — namely, anti-inflammatory, antiarrhythmic, and neuroprotective effects. The proposed molecular and cellular mechanisms include the reduction of proinflammatory cytokine levels, modulation of endothelial function, attenuation of oxidative stress, as well as favorable effects on myocardial remodeling processes and neurovascular protection. Such pleiotropic effects may play a significant pathophysiological role in slowing the progression of cardiovascular and cerebrovascular diseases, contributing to the reduction of complications and improvement of clinical outcomes. Understanding the pleiotropic properties of DOACs provides a foundation for their broader clinical application as part of integrated treatment strategies for cardiovascular, inflammatory, and cerebrovascular diseases. This review summarizes current data on the pleiotropic actions of oral anticoagulants and discusses their potential contribution to enhancing the effectiveness and individualization of pharmacotherapy in clinical cardiology.

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