Newer non-vitamin K-antagonist direct oral anticoagulants in acute coronary syndromes

standard dual antiplatelet therapy (DAPT) of aspirin and clopidogrel is associated with a substantial absolute incidence of adverse events, including death, myocardial infarction and stroke after an acute coronary syndrome (ACs). Combination therapy of an oral anticoagulant and DAPT has been previously proposed in order to improve efficacy, but has not gained popularity owing to the cumbersome management of vitamin K-antagonists (VKA). The recent introduction of newer, non-VKA, direct oral anticoagulants (NOAC), including dabigatran, apixaban, and rivaroxaban, has renewed the interest in combination therapy, owing to the more favorable pharmacokinetic and pharmacodynamic profiles of these drugs. Whereas phase II studies with dabigatran, apixaban, and rivaroxaban have consistently shown an increased bleeding risk with combination therapy, a potential increased efficacy has emerged for apixaban and rivaroxaban, thereby prompting phase III studies, namely APPRAIsE-2 with apixaban and ATLAs ACs 2-TIMI 51 with rivaroxaban. Both APPRAIsE-2 and ATLAs ACs 2-TIMI 51 studies confirmed a dose-dependent increase in major, including intracranial, bleeding with apixaban and rivaroxaban when combined with DAPT. Low-dose rivaroxaban on the other hand, was associated with significantly higher efficacy on the occurrence of combined cardiovascular death, myocardial infarction, or stroke, as well as of cardiovascular death, myocardial infarction and stent thrombosis. Owing to the persistent uncertainty regarding the net clinical benefit of combined therapy of NOAC, namely low-dose rivaroxaban, and DAPT, further studies are warranted to identify the ACs patient who will benefit most from such treatment, also in comparison to current standard DAPT of aspirin and prasugrel or ticagrelor.