title: Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome.
abstract: Objective The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS). Methods This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards. Results Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction. Conclusions In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR. Clinical Trial Registration URL: http://clinicaltrials.gov . Unique identifier: NCT01994941.
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Chor Cheung
authors.initials: CC
authors.lastname: Tam
authors.affiliation: 2 Division of Transplantation and Immunogenetics, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Janette
authors.initials: J
authors.lastname: Kwok
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wong
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Arthur
authors.initials: A
authors.lastname: Yung
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Catherine
authors.initials: C
authors.lastname: Shea
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Shun Ling
authors.initials: SL
authors.lastname: Kong
authors.affiliation: 2 Division of Transplantation and Immunogenetics, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Wing Hong
authors.initials: WH
authors.lastname: Tang
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: David
authors.initials: D
authors.lastname: Siu
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Raymond
authors.initials: R
authors.lastname: Chan
authors.affiliation: 1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000483:Alleles; D044466:Asian People; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000172:deficiency / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics* / Q000378:metabolism; D013927:Thrombosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: CYP2C19; P2Y12 receptor; acute coronary syndrome