title: Near patient anti-platelet response testing over time and gene analysis in patients admitted with acute coronary syndromes.
abstract: We sought to assess the relationships between platelet reactivity at different time points, CYP2C19*2 and ABCB1 status and clinical outcomes in patients with acute coronary syndromes (ACS). Anti-platelet response to clopidogrel was studied prospectively using the VerifyNow (VN) P2Y12 assay at the time of angiography and at 30 days post procedure in 151 patients admitted with ACS who underwent percutaneous coronary intervention (PCI). Troponin T levels were measured at angiography and 16-24 hour following PCI. DNA was extracted and the presence of CYP2C19*2 allele and ABCB1 polymorphisms were determined. Adverse cardiovascular and cerebral events (ACCE) were assessed at 12 months. High VN P2Y12 response at angiography was associated with a greater peri-procedural rise in troponin T, but not ACCE. However, VN P2Y12 response measured at 30 days was associated with ACCE (p = 0.017). CYP2C19*2 status was associated with higher VN P2Y12 response at angiography (p < 0.0001) and 30 days (p = 0.006) but not ACCE. Near-patient testing for clopidogrel response was associated with subsequent ACCE when performed 30 days following PCI, but not at angiography.
authors.affiliation: Department of Cardiology, Heart and Lung Centre, New Cross Hospital , Wolverhampton, West Midlands WV10 0QP , England.
authors.forename: Vincent
authors.initials: V
authors.lastname: Amoah
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Worrall
authors.forename: Kevin
authors.initials: K
authors.lastname: Goodridge
authors.forename: Tracy
authors.initials: T
authors.lastname: Lovatt
authors.forename: Andrew
authors.initials: A
authors.lastname: Smallwood
authors.forename: Angel L
authors.initials: AL
authors.lastname: Armesilla
authors.forename: Alan M
authors.initials: AM
authors.lastname: Nevill
authors.forename: James M
authors.initials: JM
authors.lastname: Cotton
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine