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01 December 2009

Ticagrelor--a new platelet aggregation inhibitor in patients with acute coronary syndromes. An improvement of other inhibitors?

Mariusz Kowalczyk, Maciej Banach, Dimitri P Mikhailidis, Simon Hannam, Jacek Rysz

Med Sci Monit 2009; 15(12): MS24-30 :: ID: 878263

Abstract

Antiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. Currently, clopidogrel, a second generation thienopyridine, is the main drug of choice and the combination of aspirin and clopidogrel is administered orally for the treatment of ACS. Clopidogrel, is a pro-drug that needs to be metabolized in the liver and intestines to form active metabolites. Prasugrel, a third generation thienopyridine, was approved for use in Europe in February 2009, and is currently available in the United Kingdom. All thienopyridines however, have pharmacological limitations that lead to a search for more effective non-thienopyridine P2Y12 inhibitors. Promising results have been reported with ticagrelor, an oral first reversible, direct-acting inhibitor of the P2Y12 receptor. Ticagrelor is the first oral P2Y12 receptor binding antagonist that does not require metabolic activation. Furthermore, ticagrelor has at last 1 active metabolite, which has very similar pharmacokinetics to the parent compound. Therefore, ticagrelor has more rapid onset and more pronounced platelet inhibition than other antiplatelet agents. The safety and efficacy of ticagrelor compared with clopidogrel in ACS patient has been recently evaluated by the PLATelet inhibition and patient Outcomes (PLATO) trial. Ticagrelor compared with clopidogrel had a significantly greater reduction in the death rate from vascular causes, myocardial infarction, or stroke without major bleeding. There was however, an increase in non-procedure related bleeding, dyspnoea and ventricular pauses in the first week of treatment. Further studies on new antiplatelet agents are needed to establish a new "gold standard" antiplatelet therapy.

Keywords: Thiophenes - therapeutic use, Receptors, Purinergic P2 - blood, Receptors, Purinergic P2Y12, Pyridines - therapeutic use, Purinergic P2 Receptor Antagonists, Platelet Aggregation Inhibitors - therapeutic use, Piperazines - therapeutic use, Lactones - therapeutic use, Hemorrhage - etiology, Clinical Trials as Topic, Biotransformation, Adenosine Monophosphate - therapeutic use, Adenosine - therapeutic use, Acute Coronary Syndrome - drug therapy, Ticlopidine - therapeutic use

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750