Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study.
BACKGROUND
The antiplatelet effect of aspirin is attributed to platelet cyclooxygenase-1 inhibition. Controversy exists on the prevalence of platelet resistance to aspirin in patients with coronary artery disease and effects of aspirin dose on inhibition. Our primary aim was to determine the degree of platelet aspirin responsiveness in patients, as measured by commonly used methods, and to study the relation of aspirin dose to platelet inhibition.


RESULTS
We prospectively studied the effect of aspirin dosing on platelet function in 125 stable outpatients with coronary artery disease randomized in a double-blind, double-crossover investigation (81, 162, and 325 mg/d for 4 weeks each over a 12-week period). At all doses of aspirin, platelet function was low as indicated by arachidonic acid (AA)-induced light transmittance aggregation, thrombelastography, and VerifyNow. At any 1 dose, resistance to aspirin was 0% to 6% in the overall group when AA was used as the agonist, whereas it was 1% to 27% by other methods [collagen and ADP-induced light transmittance aggregation, platelet function analyzer (PFA-100)]. Platelet response to aspirin as measured by collagen-induced light transmittance aggregation, ADP-induced light transmittance aggregation, PFA-100 (81 mg versus 162 mg, P < or = 0.05), and urinary 11-dehydrothromboxane B2 was dose-related (81 mg versus 325 mg, P = 0.003). No carryover effects were observed.


CONCLUSIONS
The assessment of aspirin resistance is highly assay-dependent; aspirin is an effective blocker of AA-induced platelet function at all doses, whereas higher estimates of resistance were observed with methods that do not use AA as the stimulus. The observation of dose-dependent effects despite nearly complete inhibition of AA-induced aggregation suggests that aspirin may exert antiplatelet properties through non-cyclooxygenase-1 pathways and deserves further investigation.
Gurbel
Paul A
PA
Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W. Belvedere Ave, Baltimore, MD 21215, USA. pgurbel@lifebridgehealth.org
Bliden
Kevin P
KP
DiChiara
Joseph
J
Newcomer
Justin
J
Weng
Willy
W
Neerchal
Nagaraj K
NK
Gesheff
Tania
T
Chaganti
Srivasavi K
SK
Etherington
Amena
A
Tantry
Udaya S
US
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology; D003327:Coronary Disease / Q000097:blood; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1 / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000379:methods; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D011446:Prospective Studies; D013916:Thrombelastography; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D051545:Cyclooxygenase 1; D001241:Aspirin