title: Determinants of high on-treatment platelet reactivity and agreement between VerifyNow and Multiplate assays.
abstract: Dual antiplatelet therapy with clopidogrel is a regimen used before and after drug-eluting stent (DES) implantation. Point-of-care platelet reactivity assays are easy-to-use methods to determine adequate response to the drug. The aim of this study was a comparison of the two platelet reactivity assays: Multiplate®and VerifyNow®and an identification of factors potentially influencing the results of these tests, including common genetic polymorphisms. The study included 39 patients receiving 75 mg clopidogrel daily before angioplasty with DES implantation. Platelet reactivity was measured with Multiplate and P2Y12VerifyNow assays. Genetic polymorphisms of CYP2C19*2, ABCB1 3435C > T, and CYP3A4*1G were determined with PCR-RFLP method and CYP2C19*17 was determined by means of an allele-specific PCR. Agreement between Multiplate and VerifyNow assays was poor (Cohen's κ = 0.056, p = .273). Hematocrit significantly negatively correlated with VerifyNow assayed platelet reactivity (r = -.487, p = .002). Female sex was significantly associated with higher VerifyNow assay results after adjustment to hematocrit (253.2 ± 47.6 PRU vs. 195.9 ± 56.9 PRU, p = .013) and the prevalence of high-on-treatment platelet reactivity (OR: 8.50; 95% CI 1.13-77.60, p = .024). Reactivity measured with Multiplate was lower in women (82.3 vs. 175.6 AU·min, p = .037) and in patients who received calcium channel blockers (74.7 vs. 191.7 AU·min, p = .002). None of the studied polymorphisms significantly influenced platelet aggregation measurements. In conclusion, different aspects modify between-patient variability of the Multiplate and VerifyNow assays and agreement between those two assays was poor.
authors.affiliation: a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Danielak
authors.affiliation: b 1st Department of Cardiology , Poznan University of Medical Sciences , Poznań , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Komosa
authors.affiliation: a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Tomczak
authors.affiliation: b 1st Department of Cardiology , Poznan University of Medical Sciences , Poznań , Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Graczyk-Szuster
authors.affiliation: b 1st Department of Cardiology , Poznan University of Medical Sciences , Poznań , Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Lesiak
authors.affiliation: a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
authors.forename: Franciszek
authors.initials: F
authors.lastname: Główka
authors.affiliation: a Department of Physical Pharmacy and Pharmacokinetics , Poznan University of Medical Sciences , Poznań , Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Karaźniewicz-Łada
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D017130:Angioplasty; D001681:Biological Assay / Q000592:standards; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D054855:Drug-Eluting Stents; D005260:Female; D015870:Gene Expression; D006400:Hematocrit; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019095:Point-of-Care Systems; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine
keywords: Genetic; hematocrit; platelet aggregation; platelet function tests; point-of-care systems; polymorphism