title: Racial disparity with on-treatment platelet reactivity in patients undergoing percutaneous coronary intervention.
abstract: BACKGROUND
  On-treatment platelet reactivity to clopidogrel is variable and in part genetic dependent. In African American (AA) patients, the relation between on-treatment platelet reactivity to clopidogrel and the factors that influence this interaction is unknown. The present study aims to evaluate on-treatment platelet reactivity to clopidogrel in AA patients and its interaction to race and CYP2C19*2 loss of function mutation.
  
  
  METHODS
  The study cohort included 289 consecutive patients presenting for percutaneous coronary intervention who were entered into a prospective observational registry. High on-treatment platelet reactivity (HTPR) was defined as P2Y12 reaction units (PRU) ≥208 with VerifyNow P2Y12 assay and >50% by vasodilator-stimulated phosphoprotein phosphorylation assay platelet reactivity index (VASP PRI) measured 6 to 24 hours postprocedure. CYP2C19*2 (rs4244285) genotype was analyzed by real-time polymerase chain reaction.
  
  
  RESULTS
  The prevalence of HTPR by both PRU (56% vs 35%, P = .003) and VASP PRI (67% vs 45%, P = .002) is more common in AAs compared with whites, respectively. African American patients had higher on-treatment mean PRU (207 ± 110 vs 160 ± 102, P = .002) and VASP PRI (49 ± 26 vs 38 ± 26, P = .004). African Americans also had a higher prevalence of CYP2C19*2 allele carrier status compared with whites (43% vs 29%, P = .04). African American race (P = .008) and CYP2C19*2 allele status (P = .02) independently had significant effects on PRU and VASP. Multivariable logistic regression analysis has shown that both CYP2C19*2 allele carrier status and AA race were independent correlates of HTPR for PRU ≥208.
  
  
  CONCLUSIONS
  African American patients undergoing percutaneous coronary intervention not only have a higher prevalence of HTPR to clopidogrel but also have higher CYP2C19*2 allele carrier status compared with whites. Careful selection of antiplatelet agents should be considered in an AA population at higher risk for ischemic complications.
authors.affiliation: Division of Cardiology, MedStar Washington Hospital Center, Washington, DC 20010, USA.
authors.forename: Lakshmana K
authors.initials: LK
authors.lastname: Pendyala
authors.forename: Rebecca
authors.initials: R
authors.lastname: Torguson
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Loh
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Devaney
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Hironori
authors.initials: H
authors.lastname: Kitabata
authors.forename: Sa'ar
authors.initials: S
authors.lastname: Minha
authors.forename: Israel M
authors.initials: IM
authors.lastname: Barbash
authors.forename: William O
authors.initials: WO
authors.lastname: Suddath
authors.forename: Lowell F
authors.initials: LF
authors.lastname: Satler
authors.forename: Augusto D
authors.initials: AD
authors.lastname: Pichard
authors.forename: Ron
authors.initials: R
authors.lastname: Waksman
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine