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

Abstract

Background Acetyl-salicylic acid (ASA) hyporesponsiveness occurs transiently after coronary artery bypass graft (CABG) surgery and may compromise the effectiveness of ASA in reducing thrombotic graft failure. A reduced response to ASA 81 mg once-daily after CABG surgery is overcome by four times daily ASA dosing. Objectives To determine whether ASA 325 mg once-daily or 162 mg twice-daily overcomes a reduced response to ASA 81 mg once-daily after CABG surgery. Methods Adults undergoing CABG surgery were randomized to ASA 81 mg once-daily, 325 mg once-daily or 162 mg twice-daily. The primary outcome was median serum thromboxane B (TXB ) level on postoperative day 4. We pooled the results with those of our earlier study to obtain better estimates of the effect of ASA 325 mg once-daily or in divided doses over 24 h. Results We randomized 68 patients undergoing CABG surgery. On postoperative day 4, patients randomized to receive ASA 81 mg once-daily had a median day 4 TXB level of 4.2 ng mL (Q1, Q3: 1.5, 7.5 ng mL ), which was higher than in those randomized to ASA 162 mg twice-daily (1.1 ng mL ; Q1, Q3: 0.7, 2.7 ng mL ) and similar to those randomized to ASA 325 mg once-daily (1.9 ng mL ; Q1, Q3: 0.9, 4.7 ng mL ). Pooled data showed that the median TXB level on day 4 in groups receiving ASA 162 mg twice-daily or 81 mg four times daily was 1.1 ng mL compared with 2.2 ng mL in those receiving ASA 325 mg once-daily. Conclusions Multiple daily dosing of ASA is more effective than ASA 81 mg once-daily or 325 mg once-daily at suppressing serum TXB formation after CABG surgery. A twice-daily treatment regimen needs to be tested in a clinical outcome study.

Quantifying immature platelets as markers of increased platelet production after coronary artery bypass grafting surgery

“…Our results show that although there is an early increase in all 3 markers post-CABG, the rise in IPC continued for at least 6 days and tracks closely with the rise in platelet count. 3,4,7 This observed correlation between the elevation in IPC and rise in platelet count is promising as it indicates that by identifying reticulated platelets, a hematology analyzer in routine use has the potential to detect a 2fold increase in platelet production.…”

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Recent studies indicate that an increased rate of platelet production (thrombopoiesis) is an important cause of reduced responsiveness to once-daily aspirin. [1][2][3][4][5][6] With accelerated thrombopoiesis, the number of "non-acetylated platelets" in the circulation increases, thereby overcoming the ability of once-daily aspirin to inhibit arachidonic acid-mediated platelet aggregation for up to 24 hours. Identifying accelerated thrombopoiesis is potentially important because the associated reduced pharmacological response is modifiable by administering aspirin twice daily.

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“…Identifying accelerated thrombopoiesis is potentially important because the associated reduced pharmacological response is modifiable by administering aspirin twice daily. [1][2][3][4]7 Three approaches have been used to identify patients with a reduced response to once-daily aspirin. 8,9 These are assays based on platelet aggregation, assays measuring thromboxane synthesis, and COX-1 acetylation assays.…”

Off‐Pump Coronary Artery Bypass Grafting: 30 Years of Debate

“…Changes in thrombopoietic indexes were largely reversible 3 months after surgery 32. As shown by 3 independent studies, shortening the dosing interval (ie, twice‐daily dosing), but not doubling the dose, safely rescued the impaired antiplatelet effect of low‐dose aspirin and prevented platelet activation associated with acute inflammation and enhanced platelet turnover following cardiac surgery 32, 36, 37…”

Antiplatelet Therapy after Coronary Artery Bypass Graft Surgery, Inconsistency of Clinical Practice and Clinical Significance of Proven Resistance to Antiplatelet Agents

“…Similar was concluded in a small low-risk cohort patients in which reduced ASA responsiveness as assessed with impedance aggregometry was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery [51]. In a randomized trial on 68 patients, it was tested whether more frequent dosing improves ASA response following CABG surgery, and it was noted that twice-daily compared with once-daily dosing reduces ASA hyporesponsiveness after CABG surgery, but the efficacy of twice-daily ASA needs to be tested in a trial powered for clinical outcomes [52]. In comparison, meta-analyses of studies consisting of patients with cardiovascular disease (not only CABG patients) suggested that patients who were resistant to aspirin were at a greater risk…”