title: Platelet reactivity after administration of third generation P2Y12-antagonists does not depend on body weight in contrast to clopidogrel.
abstract: The current standard of antiplatelet therapy for patients with myocardial infarction (MI) includes the P2Y12-receptor antagonist clopidogrel, prasugrel or ticagrelor. While it has been shown that platelet reactivity after clopidogrel administration depends on factors such as body weight, it is not known if these factors have an effect on the activity of prasugrel or ticagrelor. Thus, this study aimed to analyse factors associated with high residual platelet reactivity after administration of third generation P2Y12-antagonists compared to clopidogrel. In a single centre registry the antiplatelet effect of clopidogrel, prasugrel or ticagrelor was investigated by aggregometry in patients after MI. 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, 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)]. It was found that the r-ADP-agg correlated significantly with body weight in patients after clopidogrel administration (r = 0.423; p < 0.001). In contrast, this association was not present in patients after prasugrel (r = -0.117; p = 0.354) or ticagrelor (r = -0.082; p = 0.382) administration. Comparison of the correlation coefficients showed a significant difference (p = 0.003). In contrast to clopidogrel, platelet reactivity after administration of prasugrel or ticagrelor does not depend on body weight in patients after MI. Hence, our mechanistic data support the results of large clinical trials indicating that patients with high body weight do not need to be treated with increased doses of third generation P2Y12-antagonists to achieve sufficient platelet inhibition (registry for patients after myocardial infarction treated with antiplatelet agents; DRKS00003146).
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany. Christoph.Olivier@universitaets-herzzentrum.de.
authors.forename: Christoph B
authors.identifier: http://orcid.org/0000-0002-3065-625X
authors.initials: CB
authors.lastname: Olivier
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schnabel
authors.affiliation: Center for Medical Biometry and Medical Informatics, Medical Center - University Freiburg, Freiburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Weber
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Diehl
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D001835:Body Weight; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Aggregation; Clopidogrel; High platelet reactivity; P2Y12; Platelet; Prasugrel; Ticagrelor
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