Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study.

Published

Journal Article

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. METHODS AND 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.

Full Text

Duke Authors

Cited Authors

  • Gurbel, PA; Bliden, KP; DiChiara, J; Newcomer, J; Weng, W; Neerchal, NK; Gesheff, T; Chaganti, SK; Etherington, A; Tantry, US

Published Date

  • June 11, 2007

Published In

Volume / Issue

  • 115 / 25

Start / End Page

  • 3156 - 3164

PubMed ID

  • 17562955

Pubmed Central ID

  • 17562955

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

International Standard Serial Number (ISSN)

  • 0009-7322

Digital Object Identifier (DOI)

  • 10.1161/circulationaha.106.675587

Language

  • eng