title: Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome.
abstract: OBJECTIVE
  This study sought to investigate the evolving pattern over time of on-clopidogrel platelet reactivity (PR) and its relationship with genotype and clinical outcomes after percutaneous coronary intervention.
  
  
  BACKGROUND
  Whether on-clopidogrel PR and role of genotype differ over time is unknown.
  
  
  METHODS
  On-clopidogrel PR before percutaneous coronary intervention, and 1 and 6 months thereafter via VerifyNow P2Y12 (Accumetrics Inc., San Diego, California), CYP2C19*2, *17, CYP3A5*3, and ABCB1 polymorphisms were evaluated in 300 patients. Death, stroke, myocardial infarction, and bleedings were assessed up to 1 year.
  
  
  RESULTS
  On-clopidogrel PR varied significantly over time, being higher at baseline than at 1 and 6 months after. From baseline to 1 month, 83 of 300 patients varied their response status. This was mainly due to baseline poor responders becoming full responders (75 of 83). Genotype justifies roughly 18% of this trend. CYP2C19*2 and *17 influence on PR was consistent over time, whereas that of ABCB1 appeared of greater impact at baseline. On-clopidogrel PR at 1 month independently best predicts ischemic and bleeding events. We found a therapeutic window (86 to 238 P2Y₁₂ reactivity units) with a lower incidence of both ischemic and bleeding complications. A risk score was created by combining genotype (ABCB1 and CYP2C19*2), baseline PR, and creatinine clearance to predict 1-month poor responsiveness and 1-year poor prognosis.
  
  
  CONCLUSIONS
  In patients at steady state for clopidogrel undergoing percutaneous coronary intervention, PR decreases from baseline to 1 month. Genotype influences ≈18% of this trend. On-clopidogrel PR at 1 month is the strongest predictor of adverse outcomes, and this can be predicted by combining genotype to baseline phenotype and clinical variables.
authors.affiliation: Cardiovascular Institute, Azienda Ospedaliero-Universitaria Sant'Anna, LTTA Center, Ferrara, Italy. cmpglc@unife.it
authors.forename: Gianluca
authors.initials: G
authors.lastname: Campo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parrinello
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferraresi
authors.forename: Barbara
authors.initials: B
authors.lastname: Lunghi
authors.forename: Matteo
authors.initials: M
authors.lastname: Tebaldi
authors.forename: Matteo
authors.initials: M
authors.lastname: Miccoli
authors.forename: Jlenia
authors.initials: J
authors.lastname: Marchesini
authors.forename: Francesco
authors.initials: F
authors.lastname: Bernardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D005838:Genotype; D006801:Humans; D017202:Myocardial Ischemia / Q000235:genetics / Q000628:therapy*; D015539:Platelet Activation / Q000187:drug effects* / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine