24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease.
Aspirin-induced cyclooxygenase (COX)-1 acetylation is irreversible and it is assumed that the platelet thromboxane-A2 aggregation pathway is inhibited for at least 24 hours (h) after aspirin ingestion. However, time course of biological efficacy of daily low-dose aspirin has rarely been assessed in patients with coronary artery disease (CAD). We aimed to assess the 24-h biological efficacy of daily low-dose aspirin in CAD patients. The peak and trough (2 h-24 h) effect of a chronic treatment with once daily dose aspirin were studied in 150 consecutive stable CAD patients. The main outcome measure was light transmission aggregometry (LTA) triggered with 0.5 mg/ml arachidonic acid (AA). In the last 47 consecutive patients, additional tests were conducted at 6, 12, 16, 20 h after last aspirin administration. 4.7% of the patients had significant aggregation (>20% maximal intensity LTA-AA) 2 h after aspirin ingestion and 24.7% at 24 h (p<0.0001). The more precise assessments in the last 47 patients showed that significant platelet aggregation progressively reappeared with time after aspirin intake (2 h--4% of patients, 6 h-- 4%, 12 h--11%, 16 h--16%, 20 h--19% and 24 h--28%). Concordant results were observed using production of thromboxane-B2 and other techniques evaluating AA-induced platelet aggregation/activation. No significant differences were found between lower (75-100 mg/day) and higher (>100 mg/day) dose aspirin. Such aspirin «resistance» at 24 h after ingestion was related to biological inflammatory markers, current smoking and diabetes. In conclusion, once daily aspirin does not provide stable 24-h antiplatelet protection in a significant proportion of CAD patients. Any biological assessment of aspirin efficacy should take time since last aspirin intake into consideration.
Department of Cardiology-Lariboisiere Hospital, Assistance Publique, Hôpitaux de Paris, 2 rue A Pare, 75010 Paris, France. patrick.henry@lrb.aphp.fr
Patrick
P
Henry
Adeline
A
Vermillet
Bernadette
B
Boval
Carine
C
Guyetand
Thibaut
T
Petroni
Jean-Guillaume
JG
Dillinger
Georgios
G
Sideris
Claire
C
Bal dit Sollier
Ludovic
L
Drouet
D000368:Aged; D016718:Arachidonic Acid; D001241:Aspirin / Q000008:administration & dosage* / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010297:Paris; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013928:Thromboxane A2 / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013928:Thromboxane A2; D001241:Aspirin