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.