Dual pathway therapy in acute coronary syndrome

In 10 % of patients, who suffer an acute coronary syndrome (ACS), a major cardiovascular event occurs despite optimal therapy. The occlusion of the vessel is driven by atherothrombosis, which arises from platelet activation and activation of the coagulation cascade. In the last decade the secondary prevention continuously improved by development of dual anti-platelet therapy with new P2Y12-inhibitors such as clopidogrel, prasugrel, and ticagrelor. Until recently, the coagulation cascade was not targeted in secondary prevention. The coagulation factor Xa plays a crucial role in thrombosis and is elevated in patients after acute coronary syndrome, therefore representing an attractive target for novel therapies in ACS. Former studies with vitamin K antagonists showed reduction of cardiovascular events but increased major bleedings. Two phase-3 trials investigated the role of novel oral anticoagulant agents on top of aspirin and clopidogrel in patients with ACS. The APPRAISE-2 study, which tested the oral factor Xa inhibitor apixaban was prematurely terminated because of an increase of major bleedings in the absence of an effect on cardiovascular events. In contrast, the ATLAS ACS2 TIMI-51 trial interrogating the oral factor Xa inhibitor rivaroxaban in a low dose regimen showed significant reduction of cardiovascular events as well as total mortality. Thus, add-on treatment with low dose rivaroxaban emerged as a new option for patients with ACS. This review illustrates recent advances in the development of antithrombotic therapy in acute coronary syndromes, provides guidance on which patients should receive which therapy for secondary prevention of events, and points out potentially fruitful new strategies for the future of antithrombotic treatment in ACS.