Ticagrelor: A Cyclopentyltriazolo-pyrimidine (CPTP) Antiplatelet

Ticagrelor – a cyclopentyltriazolo-pyrimidine (CPTP) antiplatelet

Ticagrelor is a non thienopyridine antiplatelet agent belonging to a class known as cyclopentyl triazolo-pyrimidines. This binds to a site different from ADP, but blocks all the actions of ADP, acting as a reversible allosteric antagonist. It is not a prodrug and does not require activation by the liver cytochrome P450 pathway. It is rapidly absorbed after oral intake with a bioavailability of about one third and a peak plasma concentration at one and a half hours. The main metabolite is also pharmacologically active. Excretion of the drug is mainly by the hepatic route and renal excretion is less than one percent, hence does not require dose adjustment in renal disease.

PLATO trial [1] was double blind phase III trial comparing ticagrelor and clopidogrel, involving over eight hundred and sixty centers in more than forty countries. 18,624 patients with acute coronary syndrome were evaluated and there was no increased overall bleeding risk noted with ticagrelor. But there was an increase in the non coronary artery bypass related bleeding including fatal intracranial bleed. Vascular events were lesser with ticagrelor compared to clopidogrel. The offset of action is faster with ticagrelor as the action is reversible and does not need the generation of new platelets.

Reference

1. Lars Wallentin, Richard C Becker, Andrzej Budaj, Christopher P Cannon, Håkan Emanuelsson, Claes Held, Jay Horrow, Steen Husted, Stefan James, Hugo Katus, Kenneth W Mahaffey, Benjamin M Scirica, Allan Skene, Philippe Gabriel Steg, Robert F Storey, Robert A Harrington, PLATO Investigators; Anneli Freij, Mona Thorsén. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2009; 361:1045-1057.