Platelets and acute coronary syndromes Acute coronary syndromes (ACS) are the leading cause of death worldwide and one of the main reasons for hospital admissions in developed countries. ACS thus represent a major public health concern. Platelets play a pivotal role in the pathophysi- ology of ACS. They are small anuclear cell frag- ments, measuring 2-3 μm, produced in the bone marrow as a result of the fragmentation of megakaryocytes. The life span of a platelet is about 7-10 days, and around 10 11 platelets are produced every day (1) . Platelets also play an im- portant role in normal haemostasis and healing processes. CORRESPONDENCE Steen Dalby Kristensen, MD, DMSc, FESC Department of Cardiology, Aarhus University Hospital, Skejby Brendstrupgaardsvej 100, 8200 Aarhus, Denmark Phone: +45 78 45 20 30 Fax: +45 78 45 22 60 E-mail: steendk@dadlnet.dk FUNDING The authors are supported by the Danish Research Agency (grant 2101-05-0052 to Drs. Würtz, Grove, and Kristensen), Aarhus University (Dr. Würtz), and The A.P Møller Foundation for the Advancement of Medical Science (Dr. Kristensen). DISCLOSURES Dr. Kristensen has received lecture fees from AstraZeneca and Eli Lilly. Funding for this article was provided by AstraZeneca. The authors maintained full control of the content and writing of the manuscript. AstraZeneca provided medical accuracy review of the inal draft. ACKNOWLEDGEMENTS The authors appreciate the input of Ami Richards, Editor, Healthcare Bulletin in the preparation of the manuscript ISSN 2042-4884 ABSTRACT 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 pro- tection against cardiovascular outcomes than clopidogrel as evidenced by large clinical trials. This beneit might partly relect the rapid onset of action and the pronounced antiplatelet efect 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. The Antiplatelet Journey Thus Far: Focus On New Oral P2Y12 Inhibitors ACUTE CORONARY SYNDROMES | REVIEW Morten Würtz, MD, Erik Lerkevang Grove, MD, PhD, Steen Dalby Kristensen, MD, DMSc, FESC* & Sami A. Omar, MBBS, MRCP Department of Cardiology, Aarhus University Hospital, Skejby, Denmark. Received 5/9/2011, Reviewed 29/9/2011, Accepted 30/11/2011 Key words: acute coronary syndromes, antiplatelet agents, aspirin, clopidogrel, prasugrel, ticagrelor DOI: 10.5083/ejcm.20424884.62 Circulating platelets constantly interact with the vascular endothelium, but remain inactive due to the inhibitory action of e.g. nitric oxide and prostacyclin produced by endothelial cells. Upon endothelial injury, the subendothelium is exposed to the blood stream and the circulating platelet pool. This, in turn, promotes the release of mediators and cytokines that lead to the acti- vation of receptors responsible for adhesion and aggregation, such as the P2Y12, thromboxane A2 and glycoprotein IIb/IIIa receptors. Activation of these receptors induces platelet aggregation, temporarily sealing the breach in the vessel wall. Aggregated platelets provide a platform on which ibrin is incorporated once the full coagulation cascade has been activated. Regeneration of the damaged tissue is facili- tated through the release of platelet growth fac- tors. Once the healing process is complete the clot is broken down and reabsorbed (2;3) . 12 EUROPEAN JOURNAL OF CARDIOVASCULAR MEDICINE VOL II ISSUE I