Abstract 19137: Twice Daily Dosing Normalyzes the Impaired Antiplatelet Effect of Low-Dose Aspirin Due to Enhanced Platelet Turnover in Patients Undergoing On-Pump Cardiac Surgery
Previous studies reported reduced platelet cyclooxygenase (COX)-1 inhibition by once-daily (od) low-dose aspirin early after cardiac surgery.
We hypothesized that on-pump cardiac surgery enhances platelet turnover, leading to faster platelet COX-1 renewal. We measured: serum thromboxane (TX)B2 (sTXB2) and its urinary metabolite (TXM) to assess aspirin pharmacodynamics; thrombopoietin (TPO), interleukin (IL)-6, glycocalycin, immature platelet fraction (IPF), C-reactive protein to investigate the kinetics of platelet turnover. We also assessed whether a regimen of 100 mg twice-daily (bid) or 200 mg od aspirin could restore sTXB2 inhibition 7 days and 3 months post-surgery, and tested the vascular safety of these regimens, as reflected by prostacyclin (PGI2) metabolite (PGIM) excretion.
Thirty-seven patients (aged 67±6 years, 83% M) on aspirin 100 mg od were studied the day before surgery, randomized 24-36 hrs post-surgery to 100 mg od, 100 mg bid or 200 mg od for 3 months, and sampled at 8 am and 8 pm before and on day 7 post-surgery and at 3 months.
IPF, mature platelets, platelet mass, TPO, IL-6, glycocalycin, leukocytes, and C-reactive protein significantly (P<0.001) increased at day 7 post- vs. pre-surgery, with IL-6 showing a 50-fold increase. A significant (P<0.01) inverse correlation between IPF and total platelets was observed on day 7 post-surgery, consistent with enhanced thrombopoiesis.
In patients randomized to 100 mg od, the 24-h peak value of sTXB2 increased post- (3.4 [1.9-10.9] ng/mL; median [IQR]) vs. pre-surgery (2.2 [1-4.2] ng/mL, p<0.05), and evening urinary TXM almost doubled (130 [75-210] vs 244 [120-345] pg/mg creatinine, p<0.01). Patients randomized to 200 mg od had similar 24-h sTXB2 peak values pre- and 7 days post-surgery, with significantly increased TXM. Aspirin 100 mg bid lowered by ~30% sTXB2 24-h peak value post-surgery (P<0.01) and prevented TXM increase.
Urinary PGIM significantly (P<0.01) increased at day 7 post-surgery independently of the aspirin regimen.
In conclusion, a standard low-dose aspirin regimen inadequately inhibits platelet TXA2 after cardiac surgery in association with increased platelet turnover. A bid regimen restores the antiplatelet pharmacodynamics without affecting endothelial safety.
Author Disclosures: C. Patrono: Other; Modest; Speaker Fee, Astra Zeneca, Speaker Fee, Bayer Healthcare. V. Cavalca: None. B. Rocca: None. F. Veglia: None. R. De Cristofaro: None. A. Parolari: None. E. Tremoli: None.
- © 2016 by American Heart Association, Inc.