The coagulation system in atherothrombosis: Implications for new therapeutic strategies

ESSENTIALS: A State of the Art lecture “Clotting factors and atherothrombosis” was presented at the ISTH congress 2017. Coagulation proteins are not only involved in hemostasis, they also play a role in atherogenesis. Inhibition of coagulation proteins could potentially protect the vessel wall against progression of atherosclerosis. Combining antiplatelet and anticoagulant therapy has been demonstrated to improve cardiovascular outcomes in patients with stable atherosclerotic disease. Clinical manifestations of atherosclerotic disease include coronary artery disease (CAD), peripheral artery disease (PAD), and stroke. Although the role of platelets is well established, evidence is now accumulating on the contribution of coagulation proteins to the processes of atherosclerosis and atherothrombosis. Coagulation proteins not only play a role in fibrin formation and platelet activation, but also mediate various biological and pathophysiologic processes through activation of protease‐activated‐receptors (PARs). Thus far, secondary prevention in patients with CAD/PAD has been the domain of antiplatelet therapy, however, residual atherothrombotic risks remain substantial. Therefore, combining antiplatelet and anticoagulant therapy has gained more attention. Recently, net clinical benefit of combining aspirin with low‐dose rivaroxaban in patients with stable atherosclerotic disease has been demonstrated. In this review, based on the State of the Art lecture “Clotting factors and atherothrombosis” presented at the ISTH Congress 2017, we highlight the role of coagulation proteins in the pathophysiology of atherothrombosis, and specifically focus on therapeutic strategies to decrease atherothrombotic events by optimization of vascular protection.