title: Is platelet inhibition due to thienopyridines increased in elderly patients, in patients with previous stroke and patients with low body weight as a possible explanation of an increased bleeding risk?
abstract: BACKGROUND
  The TRITON-TIMI 38 study has identified three subgroups of patients with a higher risk of bleeding during treatment with the thienopyridine prasugrel: patients with a history of stroke or transient ischaemic attack (TIA), patients ≥75 years and patients with a body weight <60 kg. However, the underlying pathobiology leading to this increased bleeding risk remains to be elucidated. The higher bleeding rate may be due to a stronger prasugrel-induced inhibition of platelet aggregation in these subgroups. The aim of the present study was to determine whether on-treatment platelet reactivity is lower in these risk subgroups as compared with other patients in a large cohort on the thienopyridine clopidogrel undergoing elective coronary stenting.
  
  
  METHODS
  A total of 1069 consecutive patients were enrolled. On-clopidogrel platelet reactivity was measured in parallel by light transmittance aggregometry, the VerifyNow® P2Y12 assay and the PFA-100 collagen/ADP cartridge.
  
  
  RESULTS
  Fourteen patients (1.5%) had a prior history of stroke or TIA, 138 patients (14.5%) were older than 75 years and 30 patients (3.2%) had a body weight <60 kg. Age ≥ 75 years and a history of stroke were independent predictors of a higher on-treatment platelet reactivity. In contrast, a body weight <60 kg was significantly associated with a lower on-treatment platelet reactivity.
  
  
  CONCLUSIONS
  In two high-risk subgroups for bleeding, patients ≥ 75 years and patients with previous stroke, on-clopidogrel platelet reactivity is increased. In contrast, in patients with a low body weight, on-clopidogrel platelet reactivity is decreased, suggesting that a stronger response to a thienopyridine might only lead to more bleeds in patients with low body weight.
authors.affiliation: Department of Cardiology, St. Antonius Hospital, PO Box 2500, 3435 CM, Nieuwegein, the Netherlands.
authors.forename: N J
authors.initials: NJ
authors.lastname: Breet
authors.forename: H E
authors.initials: HE
authors.lastname: van Donkersgoed
authors.forename: J W
authors.initials: JW
authors.lastname: van Werkum
authors.forename: H J
authors.initials: HJ
authors.lastname: Bouman
authors.forename: J C
authors.initials: JC
authors.lastname: Kelder
authors.forename: F
authors.initials: F
authors.lastname: Zijlstra
authors.forename: C M
authors.initials: CM
authors.lastname: Hackeng
authors.forename: J M
authors.initials: JM
authors.lastname: Ten Berg