Background: Patients with ST-segment elevation myocardial infarction represent a high-risk population and an effective antiplatelet treatment adjunctive to primary percutaneous coronary intervention is of paramount importance. </p><p> Methods: This topic will review the current evidence on clinical efficacy and safety of oral antiplatelet therapy in patients with an acute ST-segment elevation myocardial infarction. Unsettled issues and future perspectives for their use in these patients are also discussed. </p><p> Results: Added to aspirin, clopidogrel, prasugrel and ticagrelor represent viable options regarding oral P2Y12 inhibition, with prasugrel and ticagrelor being preferred over clopidogrel, according to results of large randomized clinical trials. Early clinical efficacy of oral antiplatelet agents in STEMI patients has been questioned, mainly because of their delayed onset of action in the clinical setting of ST-segment elevation myocardial infarction and the recently described adverse effect of morphine on their pharmacodynamic/pharmacokinetic profile. Whether these agents should be administered beyond 1 year after the index event is also under discussion, as there is clinical evidence that prolonged administration may be associated with clinical benefit. </p><p> Conclusion: Use of oral P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction still faces questions and future research is needed to establish which, when and how should be administered in this clinical setting. </p><p>
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