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

To cite this article: Paikin JS, Hirsh J, Ginsberg JS, Weitz JI, Chan NC, Whitlock RP, Pare G, Johnston M, Eikelboom JW. 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; 13: 448-56. Summary. 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 ran-domized 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 throm-boxane B 2 (TXB 2) 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 TXB 2 on the second or third post-operative day, TXB 2 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 TXB 2 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 TXB 2 formation and platelet aggregation immediately following CABG surgery.

The Prevalence and Clinical Relevance of ASA Nonresponse After Cardiac Surgery: A Prospective Bicentric Study

“…Paikin et al demonstrated that the inhibition of thromboxane synthesis after CABG surgery could be improved by a higher dosage of ASA or multiple dosages of ASA per day. 34 Considering this result, a randomized dosage adjustment trial using platelet function monitoring may be helpful in the further evaluation of the question if and to what extent an individually adjusted ASA dosage represents a potentially beneficial concept for the postoperative management of patients after CABG surgery.…”

“…Paikin et al demonstrated that the response to ASA after CABG could be significantly improved by a regime with a repetitive application of ASA 4 times a day versus a single daily dosage regime. 34 Considering this, further dosage adjustment studies should use platelet function testing not only to allocate patients to a study group but also to verify the effect of a possible intervention.…”

The Effects of Different Aspirin Dosing Frequencies and the Timing of Aspirin Intake in Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review

“…Study selection was not restricted by underlying conditions (e.g., established CVD, diabetes, hypertension, dyslipidemia, essential thrombocythemia, or atrial fibrillation). Studies involving patients in an acute (postoperative) setting were not analyzed …”

“…Studies involving patients in an acute (postoperative) setting were not analyzed. [61][62][63] There were no restrictions on doses being compared provided there was a difference in dosing timing (e.g., in the morning compared to the evening) or frequency (e.g., twice or more per day vs. once per day, alternate-day vs. every day). There were no restrictions on study selection by outcome report.…”

Once versus twice daily aspirin after coronary bypass surgery: a randomized trial

“…TXB 2 is the stable metabolite of thromboxane A 2 and elevated urinary TXB 2 levels are an independent risk factor for early vein graft failure after CABG surgery . We showed that ASA 81 mg four times daily and ASA 325 mg once‐daily are more effective than ASA 81 mg once‐daily in inhibiting TXB 2 after CABG surgery . We posited that with an increased frequency of administration, ASA is able to acetylate the young platelets that escape the effects of a single 81 mg dose of the drug.…”