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Background: In patients with acute coronary syndrome (ACS), a persistent hypercoagulable state has been demonstrated and antithrombin therapy in addition to platelet inhibition has been proposed., Areas of Uncertainty: Vitamin K antagonists (VKAs) were used as oral anticoagulant (OAC) therapy and produced mixed results whereas trials are still ongoing with non-vitamin K OACs (NOACs)., Data Sources: A literature search regarding benefits and risks of different OAC therapies in ACS was conducted through MEDLINE and EMBASE (last 20 years until September 2018)., Therapeutic Advances: Patients receiving dual antiplatelet therapy (DAPT) in combination with NOAC are to be considered at high bleeding risk. Rivaroxaban 2.5 mg BID in triple therapy with DAPT, rivaroxaban 15 mg, or dabigatran 110/150 mg BID in dual therapy with P2Y12 inhibitor (mainly clopidogrel) is safer in terms of bleeding risk than triple therapy with VKA plus DAPT. The reduction in ischemic events by NOACs was most promising when added to single antiplatelet therapy. Ongoing trials with apixaban and edoxaban could clarify whether dual therapy NOACs with P2Y12 inhibitor sufficiently protect against stent thrombosis or myocardial infarction and are safer in terms of bleeding risk than a dual therapy with a VKA and clopidogrel. In the absence of randomized trials, it is unknown whether dual therapy with NOAC and aspirin could be an alternative to NOAC and a P2Y12 inhibitor. Thus, the overall benefit of adding NOAC to antiplatelet treatment after ACS in patients without clear indication for long-term OAC is still unknown., Conclusions: Different OACs have been tested as antithrombotic therapy after ACS in combination with single or DAPT and led to a modest reduction in ischemic events. Further studies evaluating NOACs in combination with single antiplatelet therapy or shorter duration of triple antithrombotic therapy are warranted.

Background: Both antiplatelets and anticoagulants are necessary in the management of acute coronary syndrome (ACS), although the exact proportion of antithrombotic effect that each drug and class should ideally provide remains a matter of ongoing study., Area of Uncertainty: Defining the best combination between the antiplatelet agents and oral anticoagulants (OACs) can be challenging. The choice is particularly important for special categories of patients with ACS who have an indication of a long-term OAC., Data Sources: A literature search regarding benefits and risks of anticoagulation in ACS was conducted through MEDLINE and EMBASE (past 20 years until September 2018)., Therapeutic Advances: Many patients with ACS have an indication for long-term OACs. Those receiving dual antiplatelet therapy and anticoagulants are considered to be at a high bleeding risk. The addition of a vitamin K antagonist (VKA) imposes a target international normalized ratio of 2.0-3.0. When non-VKA oral anticoagulants are used, the lowest effective tested dose for stroke prevention should be applied. For most patients, triple therapy in the form of an OAC plus dual antiplatelet therapy [aspirin and P2Y12 inhibitors (usually clopidogrel)] should be considered for 3-6 months. Later, dual therapy (OAC plus aspirin or clopidogrel) should be considered for an additional 6 months. After 1 year, it is recommended that only the OAC is maintained. In cases of very high bleeding risk, triple therapy can be reduced to 1 month after ACS, continuing on dual therapy up to 1 year, and thereafter only anticoagulation. In general, the bleeding risk seems to be lower with non-VKA oral anticoagulants than VKA plus antiplatelet combination., Conclusions: Many risk factors for ischemic events and bleeding overlap. The clinician's challenges include monitoring patients' adherence and global assessment of the antithrombotic effect that incorporates antiplatelet and anticoagulant effects.