Abstract
PurposeSince ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS).MethodsPlatelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACS patients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry.ResultsADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02).ConclusionTicagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.
Highlights
Patients suffering acute coronary syndromes (ACS) are routinely treated with dual antiplatelet therapy (DAPT) consisting of aspirin and an adenosine diphosphate (ADP) P2Y12 antagonist for 12 months to prevent detrimental platelet activation and subsequent atherothrombotic events [1]
Heart Association and the European Society of Cardiology [2, 3], the newer P2Y12 receptor antagonists ticagrelor and prasugrel should be preferred over clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) with stent implantation due to their more favorable effects on 1-year ischemic outcomes in large randomized clinical trials [4, 5]
Among these are toll-like receptors (TLR) and protease-activated receptors (PAR) which are not targeted by standard DAPT but might contribute to platelet hyperreactivity as well as to the development and progression of atherosclerotic cardiovascular disease [14,15,16]
Summary
Patients suffering acute coronary syndromes (ACS) are routinely treated with dual antiplatelet therapy (DAPT) consisting of aspirin and an adenosine diphosphate (ADP) P2Y12 antagonist for 12 months to prevent detrimental platelet activation and subsequent atherothrombotic events [1]. Heart Association and the European Society of Cardiology [2, 3], the newer P2Y12 receptor antagonists ticagrelor and prasugrel should be preferred over clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) with stent implantation due to their more favorable effects on 1-year ischemic outcomes in large randomized clinical trials [4, 5] The latter are most likely due to faster, stronger, and more consistent inhibition of ADP-induced platelet activation by ticagrelor and prasugrel compared to clopidogrel [4,5,6,7,8,9,10]. Among these are toll-like receptors (TLR) and protease-activated receptors (PAR) which are not targeted by standard DAPT but might contribute to platelet hyperreactivity as well as to the development and progression of atherosclerotic cardiovascular disease [14,15,16]
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