Third generation P2Y12 antagonists inhibit platelet aggregation more effectively than clopidogrel in a myocardial infarction registry

Abstract

The current standard of antiplatelet therapy of patients after myocardial infarction includes the P2Y12 receptor antagonists clopidogrel, prasugrel or ticagrelor. This study aimed to compare the antiplatelet effect of clopidogrel, prasugrel and ticagrelor in patients after myocardial infarction. In a single-centre registry the antiplatelet effect of clopidogrel, prasugrel and ticagrelor was investigated by aggregometry in patients after myocardial infarction. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 µM). To specifically quantify the effect of P2Y12 antagonists, whole blood was stimulated with 6.4 µM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP ratio to reflect an individual degree of P2Y12-dependent platelet inhibition.Platelet function of 238 patients was analysed [clopidogrel (n=58), prasugrel (n=65), ticagrelor (n=115)]. The r-ADP-agg was 35 ± 14% for patients receiving clopidogrel, 28 ± 10% for patients receiving prasugrel and 26 ± 11% for patients receiving ticagrelor. The r-ADP-agg was significantly lower in patients treated with prasugrel (p=0.0024) or ticagrelor (p<0.0001) compared to clopidogrel. There was no significant difference between patients receiving prasugrel or ticagrelor (p=0.2559). In conclusion, prasugrel and ticagrelor provide a stronger platelet inhibition compared to clopidogrel in patients after myocardial infarction. No significant difference in platelet inhibition was detected between prasugrel and ticagrelor. (registry for patients after Myocardial Infarction Treated with AntiPlatelet agents; DRKS00003146).

The Ratio of ADP- to TRAP-Induced Platelet Aggregation Quantifies P2Y12-Dependent Platelet Inhibition Independently of the Platelet Count

“…Numerous factors can influence the extent of platelet inhibition by clopidogrel [ 15 , 16 ]. Some of these factors are assay-dependent [ 13 ], which is also partly evidenced by the present study’s results. For example, presence of diabetes and proton pump inhibitor medication appeared to be more strongly associated with ADP-induced aggregation than with r-ADP-agg.…”

“…However, Iyu et al recently found that P2Y 12 -antagonists produced only minor additional inhibition of TRAP-induced aggregation and found no evidence that any of the P2Y 12 -antagonists act through other G-protein receptors including PAR1 [ 22 ]. Results from our group comparing different P2Y 12 -inhibitors showed that there are no differences of the TRAP-induced platelet aggregation in the corresponding medication group [ 13 ]. Although controversial findings exist on the influence of P2Y 12 -inhibitors TRAP-induced aggregation might be a reasonable internal control for patients under clopidogrel medication, as also stated by Gremmel et al in 2010 [ 11 , 12 ].…”

“…Multiple electrode aggregometry (MEA, Roche Diagnostics, Switzerland) was performed in whole blood of patients after percutaneous coronary intervention (PCI) under anti-platelet medication as recently described [ 13 , 14 ]. In order to assess the overall platelet aggregability, blood samples were stimulated with TRAP (Fc 32 μM).…”

“…Recently, our group showed that the ratio of ADP- to TRAP-induced platelet aggregation (r- ADP-agg) is a valuable tool reflecting a patient’s individual degree of P2Y 12 –mediated platelet reactivity and that a high r-ADP-agg is associated with an increased mortality in patients after coronary stent-implantation on clopidogrel [ 13 , 14 ]. This data suggest that r-ADP-agg might predict the clinical outcome of patients after percutaneous coronary intervention more precisely than ADP-induced platelet aggregation alone.…”

Lipopolysaccharide (LPS) induced pulmonary neutrophil recruitment and platelet activation is mediated via the P2Y1 and P2Y14 receptors in mice

“…The role of platelet purinergic receptors in the context of platelet aggregation has been well documented with co-stimulation of the P2Y1 and P2Y12 receptors by ADP, and following ATP stimulation of the P2X1 receptor [15][16][17][18][19][20][21][22]. Furthermore, a number of studies have detailed the ability of purinergic receptor stimulation to induce increases in P-selectin expression and the incidence of platelet-leukocyte conjugates which are considered to be a prerequisite for leukocyte recruitment [23][24][25].…”