Ticagrelor: A Novel Reversible Oral Antiplatelet Agent

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The complex mechanism of platelet activation creates an optimal target for pharmacological treatment in patients with acute coronary syndromes. Current antiplatelet medications that are used in addition to aspirin include the thienopyridines, clopidogrel and prasugrel, but there are several limitations to the use of these medications. Clopidogrel and prasugrel irreversibly bind to the P2Y12 receptor, creating a prolonged antiplatelet effect which can be undesirable when surgery is needed. Clopidogrel requires hepatic activation and produces variable platelet inhibition based on genetic polymorphisms. Prasugrel has more consistent platelet inhibition than clopidogrel but carries with it an increased risk of serious bleeds. Ticagrelor is a drug in a new chemical class that reversibly binds the P2Y12 receptor and noncompetitively blocks adenosine diphosphate-induced platelet activation. It was specifically designed to address the limitations of the available antiplatelet agents while maintaining comparable or better antiplatelet effects. It does not require metabolic activation and demonstrates greater platelet inhibition, a faster offset of action and comparable bleeding risk compared to clopidogrel. The pivotal PLATO (The Study of Platelet Inhibition and Patient Outcomes) trial in patients with an acute coronary syndrome demonstrated improved cardiovascular outcomes, including a reduction in myocardial infarctions and vascular events using ticagrelor as compared to clopidogrel with comparable rates of major bleeds. A puzzling finding from that trial was the lack of benefit with ticagrelor in patients enrolled from the United States, which has led to ticagrelor not being approved at this time in this country. The main adverse events with ticagrelor are bleeding and dyspnea, the latter of which is of unclear etiology and of unknown long-term clinical concern. In summary, ticagrelor is an exciting new oral antiplatelet drug that seems to be more efficacious than clopidogrel, with comparable safety. Whether issues of geographic disparities in response and the unusual side effect of dyspnea ultimately prove problematic has yet to be determined. Nonetheless, ticagrelor is a drug that has the potential to change the standard of care of patients with acute coronary syndromes.

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