title: Considerable variability in platelet activity among patients with coronary artery disease in response to an increased maintenance dose of clopidogrel.
abstract: BACKGROUND
  Variable platelet response to clopidogrel has been widely observed. Studies have shown that the mean aggregation response to clopidogrel can be changed by a higher maintenance dose. However, these studies have not focused on individual changes.
  
  
  OBJECTIVE
  This study examined the platelet function effects of increasing the maintenance clopidogrel dose from 75 to 150 mg/day with a focus on inter-individual response.
  
  
  METHODS
  Twenty patients with known coronary artery disease receiving 75 mg/day clopidogrel were recruited and given 150 mg/day clopidogrel for 30 days, then returned to 75 mg/day for an additional 30 days. Platelet function was assessed through light-transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay at baseline, 30 days, and 60 days.
  
  
  RESULTS
  Mean platelet inhibition was significantly improved with the increased maintenance dose when measured by the VerifyNow P2Y12 assay (P2Y12 reaction units: 191+/-15 vs. 158+/-17, P=0.013), but not when measured by LTA (LTA-adenosine diphosphate 5: 40+/-3 vs. 36+/-3, P = 0.11; LTA-adenosine diphosphate 20: 50+/-3 vs. 47+/-3, P = 0.23). However, only 50% of individual patients experienced improved platelet inhibition, as measured by the VerifyNow P2Y12 assay, when treated with the increased maintenance dose. Furthermore, poor baseline platelet response did not predict improved responsiveness at the increased dose.
  
  
  CONCLUSIONS
  Despite changing the population's mean antiplatelet response, an increased maintenance dose of clopidogrel did not improve antiplatelet response in a substantial number of patients; nor did baseline platelet function predict response to a higher maintenance dose.
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0293, USA.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Oestreich
authors.forename: John
authors.initials: J
authors.lastname: Holt
authors.forename: Steven P
authors.initials: SP
authors.lastname: Dunn
authors.forename: Susan S
authors.initials: SS
authors.lastname: Smyth
authors.forename: Charles L
authors.initials: CL
authors.lastname: Campbell
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.forename: Wendell S
authors.initials: WS
authors.lastname: Akers
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl