Evaluation of dose-related effects of aspirin on platelet function: Results from the aspirin-induced platelet effect (ASPECT) study

Paul A. Gurbel, Kevin P. Bliden, Joseph DiChiara, Justin Newcomer, Willy Weng, Nagaraj K. Neerchal, Tania Gesheff, Srivasavi K. Chaganti, Amena Etherington, Udaya S. Tantry

Research output: Contribution to journalArticle

Abstract

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≤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.

Original languageEnglish (US)
Pages (from-to)3156-3164
Number of pages9
JournalCirculation
Volume115
Issue number25
DOIs
StatePublished - Jun 2007

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Aspirin
Blood Platelets
Arachidonic Acid
Light
Adenosine Diphosphate
Coronary Artery Disease
Collagen
Thrombelastography
Cyclooxygenase 1
Platelet Aggregation
Outpatients
Observation

Keywords

  • Aggregation
  • Aspirin
  • Coronary disease
  • Platelets
  • Resistance

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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

Evaluation of dose-related effects of aspirin on platelet function : Results from the aspirin-induced platelet effect (ASPECT) study. / Gurbel, Paul A.; Bliden, Kevin P.; DiChiara, Joseph; Newcomer, Justin; Weng, Willy; Neerchal, Nagaraj K.; Gesheff, Tania; Chaganti, Srivasavi K.; Etherington, Amena; Tantry, Udaya S.

In: Circulation, Vol. 115, No. 25, 06.2007, p. 3156-3164.

Research output: Contribution to journalArticle

Gurbel, PA, Bliden, KP, DiChiara, J, Newcomer, J, Weng, W, Neerchal, NK, Gesheff, T, Chaganti, SK, Etherington, A & Tantry, US 2007, 'Evaluation of dose-related effects of aspirin on platelet function: Results from the aspirin-induced platelet effect (ASPECT) study', Circulation, vol. 115, no. 25, pp. 3156-3164. https://doi.org/10.1161/CIRCULATIONAHA.106.675587
Gurbel, Paul A. ; Bliden, Kevin P. ; DiChiara, Joseph ; Newcomer, Justin ; Weng, Willy ; Neerchal, Nagaraj K. ; Gesheff, Tania ; Chaganti, Srivasavi K. ; Etherington, Amena ; Tantry, Udaya S. / Evaluation of dose-related effects of aspirin on platelet function : Results from the aspirin-induced platelet effect (ASPECT) study. In: Circulation. 2007 ; Vol. 115, No. 25. pp. 3156-3164.
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abstract = "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≤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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AU - Gurbel, Paul A.

AU - Bliden, Kevin P.

AU - DiChiara, Joseph

AU - Newcomer, Justin

AU - Weng, Willy

AU - Neerchal, Nagaraj K.

AU - Gesheff, Tania

AU - Chaganti, Srivasavi K.

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AU - Tantry, Udaya S.

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N2 - 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≤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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