Role of novel and emerging oral anticoagulants for secondary prevention of acute coronary syndromes

Dual antiplatelet therapy has become a mainstay of long-term management of patients after an acute coronary syndrome (ACS). Mortality for these patients remains high despite current evidence-based treatment strategies. The coagulation cascade plays a role in the pathophysiology of ACS, and trials with warfarin in combination with dual antiplatelet therapy have found decreased rates of ischemic events at the expense of increased bleeding risk. Novel oral anticoagulants (NOACs) in the direct factor Xa (FXa) inhibitor and direct thrombin inhibitor (DTI) categories have been evaluated in combination with standard post-ACS therapy. Rivaroxaban, a FXa inhibitor, reduced the rates of ischemic events but increased major bleeding rates. Apixaban did not decrease the rates of ischemic events and also increased major bleeding rates. Other FXa inhibitors have not been studied in the long-term management of ACS (e.g., otamixaban), are not currently being studied in ongoing phase III trials (e.g., TAK-442), or have been discontinued by the manufacturer (e.g., darexaban). The DTI dabigatran had a 2- to 4-fold increased risk of major bleeding with unclear benefit for reducing ischemic events. The factor IXa inhibitor pegnivacogin is an RNA-based aptamer that has been studied in patients undergoing cardiac catheterization but has not been studied for long-term post-ACS management. The European Society of Cardiology Working Group on Thrombosis recommends the use of newer antiplatelet agents over addition of NOACs. Additional guidelines are available to guide management in patients requiring triple antithrombotic therapy but do not provide definitive recommendations on NOACs. Many questions remain about the place of NOACs for long-term post-ACS management. Recent trials have evaluated double versus triple antithrombotic therapy to balance efficacy and bleeding risk, but they did not include NOACs. It also remains unclear if NOACs hold a place in post-ACS therapy in the era of more potent antiplatelet agents such as prasugrel and ticagrelor.