Biological efficacy of low against medium dose aspirin regimen after coronary surgery: analysis of platelet function.
The failure of aspirin to inhibit platelet function has been documented in patients undergoing coronary artery bypass graft (CABG) surgery, but the causes of "aspirin-resistance" remain uncertain. The aim of this study was to investigate the efficacy of aspirin in patients undergoing CABG surgery receiving either 100 mg or 325 mg of oral aspirin for 5-days. Platelet function was tested the day before surgery and on day +1 and day +5, and evaluated by changes in collagen-induced thromboxane-A2 (TxA2) release and platelet aggregation following stimulation with collagen, ADP and epinephrine. In all patients, baseline platelet aggregation was significantly inhibited by pre-incubation with in vitro aspirin (150 micromol/l), with a mean reduction in TxA2-release of >or=95.5% (82.3,99.1). After 5-days of oral aspirin, platelet aggregation was significantly inhibited, and was not further inhibited by in vitro aspirin. Oral aspirin was also associated with a >or=99.5% (97.8, 99.7) reduction in TxA2-release, and with the reversal of the second-phase of ADP-induced aggregation which is TxA2-dependent. In addition a single-dose of 325 mg aspirin on the first post-operative morning may have a greater inhibitory effect on collagen-induced aggregation than 100 mg aspirin. Western blot analysis provided no evidence for the presence of COX-2 in platelets, while the up-regulation of p38-MAPK following platelet-stimulation and surgery was seen. The inhibition of COX-2 (NS398) or p38-MAPK (SB203580) activity did not affect platelet aggregation and TxA2-release on day +5. In summary, there was no evidence for inherent or acquired aspirin-resistance in this surgical population, or for the involvement of either COX-2 or p38-MAPK.
Cornelissen
Jacqueline
J
Department of Clinical Pharmacology, Papworth Hospital NHS Trust, Cambridge, CB3 8RE, UK. jacqueline.cornelissen@papworth.nhs.uk
Kirtland
Stephen
S
Lim
Eric
E
Goddard
Martin
M
Bellm
Sarah
S
Sheridan
Kate
K
Large
Stephen
S
Vuylsteke
Alain
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000378:metabolism; D013997:Time Factors
D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin