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

Essentials Coronary artery bypass graft (CABG) failure is associated with myocardial infarction and death. We tested whether more frequent dosing improves aspirin (ASA) response following CABG surgery. Twice-daily compared with once-daily dosing reduces ASA hyporesponsiveness after CABG surgery. The efficacy of twice-daily ASA needs to be tested in a trial powered for clinical outcomes. SUMMARY: 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 B₂ (TXB₂ ) 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 TXB₂ level of 4.2 ng mL^-1 (Q1, Q3: 1.5, 7.5 ng mL^-1 ), which was higher than in those randomized to ASA 162 mg twice-daily (1.1 ng mL^-1 ; Q1, Q3: 0.7, 2.7 ng mL^-1 ) and similar to those randomized to ASA 325 mg once-daily (1.9 ng mL^-1 ; Q1, Q3: 0.9, 4.7 ng mL^-1 ). Pooled data showed that the median TXB₂ level on day 4 in groups receiving ASA 162 mg twice-daily or 81 mg four times daily was 1.1 ng mL^-1 compared with 2.2 ng mL^-1 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 TXB₂ formation after CABG surgery. A twice-daily treatment regimen needs to be tested in a clinical outcome study.