title: Multiple daily doses of acetyl-salicylic acid (ASA) overcome reduced platelet response to once-daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial.
abstract: BACKGROUND
  The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post-operative platelet turnover.
  
  
  OBJECTIVE
  To determine whether acetyl-salicylic acid (ASA) 325 mg once-daily or 81 mg four-times daily overcomes the impaired response to ASA 81 mg once-daily in post-operative coronary artery bypass graft (CABG) patients.
  
  
  METHODS
  We randomized 110 patients undergoing CABG surgery to either ASA 81 mg once-daily, 81 mg four times daily or 325 mg once-daily and compared their effects on serum thromboxane B2 (TXB2 ) suppression and arachidonate-induced platelet aggregation.
  
  
  RESULTS
  One hundred patients were included in the final analysis. Platelet counts fell after surgery, reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB2 on the second or third post-operative day, TXB2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once-daily and less evident in those receiving ASA four times daily. On post-operative day 4, (i) median TXB2 levels were lower with four times daily ASA than with either ASA 81 mg once-daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P < 0.0001) or ASA 325 mg once-daily (3.4 ng/mL; Q1,Q3: 2.0, 8.2 ng/mL; P = 0.002), and (ii) ASA given four times daily was more effective than ASA 81 mg once-daily and 325 mg once-daily at suppressing platelet aggregation.
  
  
  CONCLUSIONS
  Four times daily ASA is more effective than ASA 81 and 325 mg once-daily at suppressing serum TXB2 formation and platelet aggregation immediately following CABG surgery.
authors.affiliation: Hamilton General Hospital, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Paikin
authors.forename: J
authors.initials: J
authors.lastname: Hirsh
authors.forename: J S
authors.initials: JS
authors.lastname: Ginsberg
authors.forename: J I
authors.initials: JI
authors.lastname: Weitz
authors.forename: N C
authors.initials: NC
authors.lastname: Chan
authors.forename: R P
authors.initials: RP
authors.lastname: Whitlock
authors.forename: G
authors.initials: G
authors.lastname: Pare
authors.forename: M
authors.initials: M
authors.lastname: Johnston
authors.forename: J W
authors.initials: JW
authors.lastname: Eikelboom
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001026:Coronary Artery Bypass / Q000009:adverse effects; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010976:Platelet Count; D010979:Platelet Function Tests; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D001241:Aspirin
keywords: aspirin; coronary artery bypass; drug resistance; perioperative period; platelet function tests