Interv Akut Kardiol. 2011;10(3):128-136

Ticagrelor - first reversible inhibitor of ADP receptor P2Y12

Jan Bultas

Farmakologický ústav 3. LF UK Praha

Antiplatelet therapy based on the inhibition of the platelet P2Y12 receptor for adenosine diphosphate (ADP) along with the inhibition

of thromboxane A2 production by acetylsalicylic acid is among the well-established therapeutic approaches for reducing thrombotic

complications in patients at a high risk. The use of the gold standard – clopidogrel – is associated with an approximately 30 % rate of

resistance to treatment when there is polymorphism in the bioactivating enzymes. This fact has resulted in the introduction of new and

more reliable inhibitors of ADP receptors. Ticagrelor is the first of a new generation of non-thienopyridine reversible inhibitors of ADP

receptors P2Y12. The inhibition of the receptor is mediated to a greater degree by the parent substance, to a lesser degree by the active

metabolite. Following oral administration, ticagrelor resorbs rapidly and stably with a rapid onset of action of 30 to 60 minutes; the elimination

half-life ranges from 6 to 13 hours. It is biodegraded by the CYP3A4 isoenzyme and excreted by the liver into bile. The reversibility

of the inhibition and an effect confined to 12–24 hours result, on one hand, in greater demands for patient compliance; however, on the

other hand, greater safety is achieved in the case of bleeding or when an intervention is required. The efficacy and safety of ticagrelor

have been tested in a number of trials; however, the results of the PLATO trial are of decisive importance. This morbidity/mortality trial

compared the effect of ticagrelor with that of clopidogrel in patients with acute coronary events (of the STEMI and non-STEMI type).

Ticagrelor was given at a loading dose of 180 mg, followed by maintenance doses of 90 mg twice a day; clopidogrel was given at a loading

dose of 300 or 600 mg and a maintenance dose of 75 mg once a day. Nearly all the patients (94 %) were also treated with acetylsalicylic

acid. The duration of treatment was 6 to 12 months. A significant reduction in the combined endpoint (cardiovascular mortality and

nonfatal myocardial infarction or stroke) was demonstrated, with a decrease by 16 % compared to clopidogrel; the same decrease was

noted when cardiovascular mortality was replaced by overall mortality. In patients with stent implantation as part of primary intervention,

the rate of thrombotic stent occlusion decreased by 33 % with ticagrelor treatment. In terms of safety, there was no increase in

bleeding episodes in any of the categories (severe, life-threatening or fatal). When indicated to prevent thrombotic episodes in patients

with acute coronary events such as angina pectoris and non-ST segment elevation myocardial infarction (non-STEMI events) or with ST

segment elevation myocardial infarction (STEMI events), ticagrelor has been approved for use, optimally in combination with acetylsalicylic

acid, at a dose of 90 mg twice a day.

Keywords: ticagrelor, antiplatelet drugs, acute coronary syndromes, inhibitors of ADP receptor P2Y12

Published: June 10, 2011  Show citation