title: Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation. An ADAPT-DES substudy.
abstract: Given conflicting data on temporal variability in pharmacodynamic platelet responses to clopidogrel, we investigated platelet reactivity on clopidogrel and aspirin for up to six months after elective percutaneous coronary intervention (PCI) with drug-eluting stents. Platelet reactivity was determined in 102 patients before loading with clopidogrel and aspirin, and on maintenance therapy after PCI on day 1, at one month and six months by VerifyNow™ P2Y12 and Aspirin assays and by residual platelet aggregation (RPA) on light transmission aggregometry using adenosine diphosphate and arachidonic acid. By VerifyNow testing, median (interquartile range) P2Y12 reaction units (PRU) on clopidogrel were 166 (90-234), 195 (124-257), and 198 (141-252) on day 1, one month and six months after PCI, respectively (p=0.005 day 1 to 1 month, and p=0.86 1 month to 6 months). Using a cut-off of > 208 PRU, 35 % of patients had high platelet reactivity (HPR) to clopidogrel on day 1, 43 % at one month, and 46 % at six months after PCI. Between day 1 and six months after PCI, 38.2 % of patients changed clopidogrel responder status at least once. Other cut-offs and RPA yielded similar results. Platelet inhibition by aspirin was consistent over time with only five patients being characterised as having HPR. Considerable variation in individual on-clopidogrel platelet reactivity was present during both the subacute and the late phases of maintenance therapy after elective PCI. Hence, the utility of contemporary platelet function testing to guide antiplatelet therapy may be limited.
authors: Thomas G. Nührenberg, Universitäts-Herzzentrum Freiburg - Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, 79189 Bad Krozingen, Germany, Tel.: +49 7633 4841, Fax: +49 761 402 2489, E-mail: thomas.nuehrenberg@universitaets-herzzentrum.de.
authors: Thomas G
authors: TG
authors: Nührenberg
authors: Christian
authors: C
authors: Stratz
authors: Stefan
authors: S
authors: Leggewie
authors: Willibald
authors: W
authors: Hochholzer
authors: Christian M
authors: CM
authors: Valina
authors: Michael
authors: M
authors: Gick
authors: Ajay J
authors: AJ
authors: Kirtane
authors: Gregg W
authors: GW
authors: Stone
authors: Franz-Josef
authors: FJ
authors: Neumann
authors: Dietmar
authors: D
authors: Trenk
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D019917:Blood Vessel Prosthesis Implantation; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000601:surgery; D054855:Drug-Eluting Stents / Q000706:statistics & numerical data; D017558:Elective Surgical Procedures; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D010979:Platelet Function Tests; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: ADAPT-DES; Clopidogrel; VerifyNow™; drug-eluting stent; platelet reactivity