title: Effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis after coronary artery bypass graft surgery.
abstract: OBJECTIVE
  The purpose of this study was to determine if an incomplete response to or inadequate antiplatelet effect of aspirin, or both, contribute to saphenous vein graft (SVG) occlusion after coronary artery bypass graft (CABG) surgery.
  
  
  BACKGROUND
  Thrombosis is the predominant cause of early SVG occlusion. Aspirin, which inhibits cyclooxygenase-1 activity and thromboxane generation in platelets, reduces early SVG occlusion by one-half.
  
  
  METHODS
  Aspirin responsiveness and platelet reactivity were characterized 3 days and 6 months after coronary artery bypass graft surgery in 229 subjects receiving aspirin monotherapy by platelet aggregation to arachidonic acid, adenosine diphosphate, collagen and epinephrine, Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Newark, Delaware) closure time (CT) using collagen/epinephrine agonist cartridge and collagen/adenosine diphosphate (CADP) agonist cartridge, VerifyNow Aspirin assay (Accumetrics, Inc., San Diego, California), and urine levels of 11-dehydro-thromboxane B(2) (UTXB(2)). SVG patency was determined 6 months after surgery by computed tomography coronary angiography.
  
  
  RESULTS
  Inhibited arachidonic acid-induced platelet aggregation, indicative of aspirin-mediated cyclooxygenase-1 suppression, occurred in 95% and >99% of subjects 3 days and 6 months after surgery, respectively. Despite this, 73% and 31% of subjects at these times had elevated UTXB(2). Among tested parameters, only UTXB(2) and CADP CT measured 6 months after surgery correlated with outcome. By multivariate analysis, CADP CT of ≤88 s (odds ratio: 2.85, p = 0.006), target vessel diameter of ≤1.5 mm (odds ratio: 2.38, p = 0.01), and UTXB(2) of ≥450 pg/mg creatinine (odds ratio: 2.59, p = 0.015) correlated with SVG occlusion. CADP CT and UTXB(2) in combination further identified subjects at particularly high and low risk for SVG occlusion.
  
  
  CONCLUSIONS
  Aspirin-insensitive thromboxane generation measured by UTXB(2) and shear-dependent platelet hyper-reactivity measured by Platelet Function Analyzer-100 CADP CT are novel independent risk factors for early SVG thrombosis after coronary artery bypass graft surgery.
authors.affiliation: Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Gluckman
authors.forename: Rhondalyn C
authors.initials: RC
authors.lastname: McLean
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schulman
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kickler
authors.forename: Edward P
authors.initials: EP
authors.lastname: Shapiro
authors.forename: John V
authors.initials: JV
authors.lastname: Conte
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: McNicholas
authors.forename: Jodi B
authors.initials: JB
authors.lastname: Segal
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Rade
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D017023:Coronary Angiography; D001026:Coronary Artery Bypass / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count; D012501:Saphenous Vein / Q000637:transplantation*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin