The Antiplatelet Journey Thus Far: Focus On New Oral P2Y12-Inhibitors

Platelets are pivotal in the pathophysiology of acute coronary syndromes; the leading cause of death worldwide. The use of antiplatelet agents in the treatment of acute coronary syndromes has reduced morbidity and mortality substantially. Thus, aspirin has been a cornerstone in the treatment of acute coronary syndromes for years. However, during the last decade the P2Y12-inhibitor clopidogrel has accompanied aspirin to further improve clinical outcomes. P2Y12-inhibitors are antiplatelet agents preventing the binding of adenosine diphosphate to P2Y12-receptors on the platelet surface thus inhibiting platelet aggregation.Recently, the emergence of two new P2Y12-inhibitors, prasugrel and ticagrelor, has challenged the role of clopidogrel. Similar to clopidogrel, prasugrel is a prodrug that needs hepatic conversion to its active metabolite to provide irreversible P2Y12-inhibition. In contrast, ticagrelor is a direct-acting allosteric P2Y12-antagonist inhibiting the P2Y12-receptor reversibly. Both drugs provide a better protection against cardiovascular outcomes than clopidogrel as evidenced by large clinical trials. This benefit might partly reflect the rapid onset of action and the pronounced antiplatelet effect of these drugs compared to clopidogrel. So far, no direct comparison of prasugrel and ticagrelor has been performed, but ongoing trials will provide data to clarify the clinical role of these drugs.The present review outlines the key milestones of the history of P2Y12-inhibitors and provides an up-to-date overview and comparison of the clinical applicability of these drugs.