title: High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention.
abstract: OBJECTIVE
  High on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) are associated with atherothrombotic events following coronary stenting. There are, however, few data concerning high on-treatment platelet reactivity to both aspirin and clopidogrel simultaneously. The aim of the present study was to determine the incidence of dual high on-treatment platelet reactivity (DAPR) and its impact on clinical outcome.
  
  
  METHODS
  On-treatment platelet reactivity was measured in parallel by ADP- and arachidonic acid-induced light transmittance aggregometry (LTA) (n=921) and the point-of-care VerifyNow system (P2Y12 and aspirin) (n=422) in patients on dual antiplatelet therapy undergoing elective stent implantation. HCPR and HAPR were established by receiver-operator characteristic curve analysis. The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischaemic stroke at 1-year follow-up.
  
  
  RESULTS
  The incidence of DAPR varied between 14.7% and 26.9% depending on the platelet function test used. DAPR, assessed by LTA and the VerifyNow system, was highly associated with an adverse clinical outcome. At 1-year follow-up the primary endpoint occurred more frequently in patients with isolated HCPR (11.7%), isolated HAPR (9.6%) or DAPR (10.7%) compared with patients without high on-treatment platelet reactivity (4.2%, all p<0.01) when platelet function was evaluated with LTA. Using the VerifyNow system, patients exhibiting DAPR had the highest risk for the primary endpoint (17.7% vs 4.1% in patients without high on-treatment platelet reactivity, p=0.001).
  
  
  CONCLUSIONS
  In patients undergoing elective percutaneous coronary intervention, DAPR to aspirin and clopidogrel is present in one in five patients and is associated with a high risk for atherothrombotic events. DAPR measured by the point-of-care VerifyNow system has a higher predictability for atherothrombotic events than LTA.
  
  
  BACKGROUND
  www.clinicaltrials.gov: NCT00352014.
authors.affiliation: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Nicoline J
authors.initials: NJ
authors.lastname: Breet
authors.forename: Jochem W
authors.initials: JW
authors.lastname: van Werkum
authors.forename: Heleen J
authors.initials: HJ
authors.lastname: Bouman
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Kelder
authors.forename: Ankie M
authors.initials: AM
authors.lastname: Harmsze
authors.forename: Christian M
authors.initials: CM
authors.lastname: Hackeng
authors.forename: Jurriën M
authors.initials: JM
authors.lastname: ten Berg
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000009:adverse effects*; D050197:Atherosclerosis / Q000139:chemically induced*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006083:Graft Occlusion, Vascular / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D012307:Risk Factors; D015607:Stents; D020521:Stroke / Q000139:chemically induced; D013927:Thrombosis / Q000139:chemically induced*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin