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

Publication ,  Journal Article
Gurbel, PA; Bliden, KP; DiChiara, J; Newcomer, J; Weng, W; Neerchal, NK; Gesheff, T; Chaganti, SK; Etherington, A; Tantry, US
Published in: Circulation
June 26, 2007

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.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

June 26, 2007

Volume

115

Issue

25

Start / End Page

3156 / 3164

Location

United States

Related Subject Headings

  • Thromboxane B2
  • Thrombelastography
  • Prospective Studies
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Function Tests
  • Platelet Aggregation Inhibitors
  • Platelet Aggregation
  • Nephelometry and Turbidimetry
  • Middle Aged
  • Male
 

Citation

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Gurbel, P. A., Bliden, K. P., DiChiara, J., Newcomer, J., Weng, W., Neerchal, N. K., … Tantry, U. S. (2007). Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation, 115(25), 3156–3164. https://doi.org/10.1161/CIRCULATIONAHA.106.675587
Gurbel, Paul A., Kevin P. Bliden, Joseph DiChiara, Justin Newcomer, Willy Weng, Nagaraj K. Neerchal, Tania Gesheff, Srivasavi K. Chaganti, Amena Etherington, and Udaya S. Tantry. “Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study.Circulation 115, no. 25 (June 26, 2007): 3156–64. https://doi.org/10.1161/CIRCULATIONAHA.106.675587.
Gurbel PA, Bliden KP, DiChiara J, Newcomer J, Weng W, Neerchal NK, et al. Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation. 2007 Jun 26;115(25):3156–64.
Gurbel, Paul A., et al. “Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study.Circulation, vol. 115, no. 25, June 2007, pp. 3156–64. Pubmed, doi:10.1161/CIRCULATIONAHA.106.675587.
Gurbel PA, Bliden KP, DiChiara J, Newcomer J, Weng W, Neerchal NK, Gesheff T, Chaganti SK, Etherington A, Tantry US. Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation. 2007 Jun 26;115(25):3156–3164.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

June 26, 2007

Volume

115

Issue

25

Start / End Page

3156 / 3164

Location

United States

Related Subject Headings

  • Thromboxane B2
  • Thrombelastography
  • Prospective Studies
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Function Tests
  • Platelet Aggregation Inhibitors
  • Platelet Aggregation
  • Nephelometry and Turbidimetry
  • Middle Aged
  • Male