Current antithrombotic agents for acute coronary syndromes: focus on bleeding risk

Abstract

The formation of an intravascular thrombus underlies the clinical symptoms associated with acute coronary syndromes (ACS). Plaque rupture signals the recruitment and activation of platelets, initiation of the coagulation cascade, and generation of thrombin, resulting in the formation of a platelet-rich thrombus. Use of antithrombotic therapy, including antiplatelet and anticoagulant agents, is a crucial element in reducing the overall morbidity and mortality in patients with ACS. Current antiplatelet and anticoagulant therapies act on distinct sites in platelet activation pathways and the coagulation cascade, but because these agents target pathways necessary for protective hemostasis, their use increases the risk for bleeding complications. Previously, bleeding was considered an unavoidable side effect of ACS management with few clinical implications; however, bleeding has since been shown to be an independent predictor of short- and long-term mortality in patients with ACS. Therefore, the prevention of bleeding has become equally as important as the prevention of further ischemic events. Strategies to limit bleeding include bleeding risk stratification, appropriate dosing of antithrombotic drugs, use of the lowest dose of aspirin with proven efficacy, avoidance of combinations of antithrombotic agents unless for a proven indication, use of drugs proven to reduce the risk of bleeding, and choice of radial access over femoral access in case of invasive strategy. In this context, several novel therapeutic approaches are currently under clinical evaluation, including new antiplatelet agents, such as protease-activated receptor 1 antagonists, and new anticoagulants, such as direct-acting antagonists of factor Xa and factor IIa (thrombin). This review discusses antiplatelet and anticoagulant treatment strategies for the management of ACS, with a particular focus on their associated bleeding risks.