Targeting therapy to the fibrin-mediated pathophysiology of acute coronary syndrome.

Acute coronary syndrome (ACS) encompasses a spectrum of diseases, ranging from ST-elevation myocardial infarction to non-ST-elevation myocardial infarction and unstable angina. A key initiating event in the pathology of ACS is atheromatous plaque disruption, in which the exposure of thrombogenic material triggers simultaneous activation of primary and secondary hemostatic pathways. Targeting platelet-mediated thrombus formation with dual antiplatelet therapy comprising acetylsalicylic acid and a P2Y12 antagonist is the current mainstay for management of ACS. However, a significant proportion of patients remain at risk of cardiovascular events. Fibrin is an important contributor to thrombogenesis and may account for the residual event rates. This review examines evidence for the role of the coagulation cascade in thrombus formation in ACS, which provides a rationale for the use of anticoagulation therapy. The current status of research with novel oral anticoagulants in combination with dual antiplatelet therapy for the secondary prevention of ACS is also discussed.