title: Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease.
abstract: BACKGROUND
  Aspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported.
  
  
  OBJECTIVE
  To investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients.
  
  
  METHODS
  We performed a cross-sectional study including 900 stable, high-risk CAD patients. Among these, 795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170 (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. The antiplatelet effect of aspirin was assessed by measurement of platelet aggregation employing 1) multiple electrode aggregometry (MEA, Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay. Compliance was assessed by measurement of serum thromboxane B2.
  
  
  RESULTS
  Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased AA-induced MEA platelet aggregation in citrate and hirudin anticoagulated blood (p-values ≤ 0.045). Similar results were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent determinants of increased platelet aggregation (p-values ≤ 0.038). Compliance was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml).
  
  
  CONCLUSIONS
  Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased platelet aggregation, indicating that these characteristics may be key factors in reduced antiplatelet effect of aspirin in stable CAD patients.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Sanne Bøjet
authors.initials: SB
authors.lastname: Larsen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Erik Lerkevang
authors.initials: EL
authors.lastname: Grove
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søs
authors.initials: S
authors.lastname: Neergaard-Petersen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Würtz
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
authors.forename: Anne-Mette
authors.initials: AM
authors.lastname: Hvas
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
authors.forename: Steen Dalby
authors.initials: SD
authors.lastname: Kristensen
mesh_terms: D000368:Aged; D001241:Aspirin / Q000097:blood*; D015992:Body Mass Index; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000188:drug therapy; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D001241:Aspirin