AMSTERDAM – Giving low-dose aspirin four times per day in the first days after coronary artery bypass graft surgery suppresses serum thromboxane levels far more effectively than does conventional once-daily dosing at 325 mg, according to a randomized trial.
The clinical implication of this finding is that more frequent dosing of aspirin may prevent the serious problem of premature vein graft failure from the development of aspirin resistance in the postoperative period, although at this point this is a hypothesis that requires testing in a future study, Dr. Jeremy S. Paikin said at the annual congress of the European Society of Cardiology.
Dr. Jeremy Paikin
He reported on 110 on-pump coronary artery bypass graft (CABG) patients randomized on postoperative day 1 to aspirin either at 81 mg four times daily, the standard 325 mg once daily, or to 81 mg once daily.
The primary study endpoint was the serum thromboxane level on the morning of postoperative day 4. The median level was 13.3 ng/mL in the group on aspirin at 81 mg once daily, 3.4 ng/mL with 325 mg once daily, and significantly lower at 1.1 ng/mL in patients on 81 mg four times daily.
"With 81 mg QD [four times daily], there’s almost complete suppression of serum thromboxane throughout the course of the hospital stay," according to Dr. Paikin of McMaster University, Hamilton, Ont.
Aspirin is known to prevent CABG graft failure, but its effectiveness is limited by the not-infrequent development of aspirin hyporesponsiveness in the postoperative period. The underlying mechanism involved in this aspirin resistance was previously unknown; however, in their randomized trial Dr. Paikin and coinvestigators established that the hyporesponsiveness is caused at least in part by increased platelet turnover in the postoperative period. The investigators showed that platelet turnover per day was increased two- to threefold in the week after CABG, compared with presurgical levels, a finding Dr. Paikin termed "quite exciting."
Recognizing that administration of any drug four times daily raises formidable adherence obstacles, he and his coworkers are just about to start a clinical trial looking at twice-daily aspirin dosing post CABG. They’re also interested in drawing a firm evidentiary connection between serum thromboxane levels and risk of premature graft failure.
Dr. Paikin reported having no financial conflicts of interest.