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

J Thromb Haemost. 2015 Mar;13(3):448-56. doi: 10.1111/jth.12832. Epub 2015 Feb 6.


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.

Objectives: 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.

Keywords: aspirin; coronary artery bypass; drug resistance; perioperative period; platelet function tests.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Coronary Artery Bypass* / adverse effects
  • Drug Administration Schedule
  • Drug Resistance
  • Female
  • Humans
  • Male
  • Middle Aged
  • Ontario
  • Pilot Projects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Count
  • Platelet Function Tests
  • Thromboxane B2 / blood
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Thromboxane B2
  • Aspirin