title: A study on the impact of CYP2C19 genotype and platelet reactivity assay on patients undergoing PCI.
abstract: BACKGROUND
  A thorough understanding of the patient's genotype and their functional response to a medication is necessary for improving event free survival. Several outcome studies support this view particularly if the patient is to be started on clopidogrel due to the prevalence of clopidogrel resistance. Such guided therapy has reduced the incidence of Major Adverse Cardiac Events (MACE) after stent implantation.
  
  
  METHODS
  Between August 2013 and August 2014, 200 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) were prescribed any one of the anti-platelet medications such as clopidogrel, prasugrel or ticagrelor and offered testing to detect CYP2C19 gene mutations along with a platelet reactivity assay (PRA). Intended outcome was modification of anti-platelet therapy defined as either dose escalation of clopidogrel or replacement of clopidogrel with prasugrel or ticagrelor for the patients in clopidogrel arm, and replacement of ticagrelor or prasugrel with clopidogrel if those patients were non-carrier of mutant genes and also if they demonstrated bleeding tendencies in the ticagrelor and prasugrel arms.
  
  
  CONCLUSIONS
  Clopidogrel resistance was observed to be 16.5% in our study population. PRA was useful in monitoring the efficacy of thienopyridines. By having this test, one can be safely maintained on clopidogrel in non-carriers, or with increased dose of clopidogrel in intermediate metabolizers or with newer drugs such as ticagrelor or prasugrel in poor metabolizers. Patients on ticagrelor and prasugrel identified as non-carriers of gene mutations for clopidogrel metabolism could be offered clopidogrel resulting in economic benefits to the patients. Patients at high risk of bleeding were also identified by the PRA.
authors.affiliation: Director of Cardiology & Cath Lab, Apollo Hospital, Jubilee Hills, Hyderabad, India. Electronic address: drpcrath@hotmail.com.
authors.forename: P C
authors.initials: PC
authors.lastname: Rath
authors.affiliation: Apollo Hospital, Jubilee Hills, Hyderabad, India.
authors.forename: Sundar
authors.initials: S
authors.lastname: Chidambaram
authors.affiliation: Apollo Hospital Education and Research Foundation, Apollo Health City, Hyderabad, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Rath
authors.affiliation: Apollo Hospital, Jubilee Hills, Hyderabad, India.
authors.forename: Byomakesh
authors.initials: B
authors.lastname: Dikshit
authors.affiliation: Apollo Hospital, Jubilee Hills, Hyderabad, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Naik
authors.affiliation: Apollo Hospital, Bhubaneswar, India.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Sahoo
authors.affiliation: Apollo Hospital, Bhubaneswar, India.
authors.forename: Brajraj
authors.initials: B
authors.lastname: Das
authors.affiliation: Sapiens Biosciences Pvt Ltd, Apollo Health City, Jubilee Hills, Hyderabad, India.
authors.forename: Mohanshankar
authors.initials: M
authors.lastname: Mahalingam
authors.affiliation: Sapiens Biosciences Pvt Ltd, Apollo Health City, Jubilee Hills, Hyderabad, India.
authors.forename: Lakshmipathi
authors.initials: L
authors.lastname: Khandrika
authors.affiliation: Sapiens Biosciences Pvt Ltd, Apollo Health City, Jubilee Hills, Hyderabad, India.
authors.forename: Jugnu
authors.initials: J
authors.lastname: Jain
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000628:therapy; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062645:Percutaneous Coronary Intervention; D015539:Platelet Activation / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D012189:Retrospective Studies; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D004247:DNA; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: CYP2C19 genotype; PCI; Platelet reactivity assay