Direct oral anticoagulants in acute coronary syndrome

Patients with acute coronary syndromes (ACS) require a specific antithrombotic therapy in the immediate and the post ACS phase. The current antithrombotic therapy in the acute phase of an ACS combines antiplatelet and anticoagulant drugs in order to reduce ischemic cardiovascular events. In the post ACS phase, dual antiplatelet therapy (DAPT; aspirin and a P2Y12 receptor antagonist) is the current mainstay of antithrombotic treatment and is recommended in the guidelines of the major North American and European clinical cardiology associations (AHA, ACC, and ESC). Recently, the addition of rivaroxaban, a low dose oral direct factor Xa inhibitor (2.5 mg twice daily), to DAPT (aspirin plus second-generation P2Y12 inhibitor) showed a significant reduction of cardiovascular and overall mortality in the major phase III clinical trial ATLAS ACS 2 TIMI 51. This led to the approval of low-dose rivaroxaban in addition to aspirin and clopidogrel by the European Medicines Agency (EMA) in 2013. Other direct oral anticoagulants (apixaban, dabigatran etexilate) have also been assessed in phase II (dabigatran etexilate) and phase III (apixaban) post ACS clinical trials. In the studied dosing regimens, these drugs failed to show a net clinical benefit in addition to dual antiplatelet therapy. The major clinical phase II and III post ACS studies of direct oral anticoagulants are summarized and discussed in this article along with the concept of long-term anticoagulation for the secondary prevention of ischemic events after ACS and implications for the future of antithrombotic therapy in the current era of third-generation P2Y12 receptor inhibitors (Prasugrel and Ticagrelor).