This Article Full Text Full Text (PDF) CME: Take the course for this article: Circulation: June 26, 2007, Volume 115, Number 25 All Versions of this Article: 115/25/3156    most recent CIRCULATIONAHA.106.675587v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gurbel, P. A. Articles by Tantry, U. S. Search for Related Content PubMed PubMed Citation Articles by Gurbel, P. A. Articles by Tantry, U. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ACETYLSALICYLIC ACID Medline Plus Health Information Blood Thinners Related Collections Aggregation Acute coronary syndromes Platelets Related Article

(Circulation. 2007;115:3156-3164.)
© 2007 American Heart Association, Inc.

Coronary Heart Disease

Evaluation of Dose-Related Effects of Aspirin on Platelet Function

Results From the Aspirin-Induced Platelet Effect (ASPECT) Study

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

From the Sinai Center for Thrombosis Research, Baltimore, Md (P.A.G., K.P.B., J.D., T.G., S.K.C., A.E., U.S.T.), and the Department of Mathematics and Statistics (J.N., W.W., N.K.N.), University of Maryland Baltimore County, Baltimore.

Correspondence to Paul A. Gurbel, MD, Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W. Belvedere Ave, Baltimore, MD 21215. E-mail pgurbel{at}lifebridgehealth.org

Received October 5, 2006; accepted April 23, 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, P0.05), 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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Issue Highlights
Circulation 2007 115: 3139. [Extract] [Full Text]

This article has been cited by other articles:

				M. C. Wesley, F. X. McGowan, R. A. Castro, S. Dissanayake, D. Zurakowski, and J. A. DiNardo The Effect of Milrinone on Platelet Activation as Determined by TEG(R) Platelet MappingTM Anesth. Analg., May 1, 2009; 108(5): 1425 - 1429. [Abstract] [Full Text] [PDF]

				D. J. Angiolillo Antiplatelet Therapy in Diabetes: Efficacy and Limitations of Current Treatment Strategies and Future Directions Diabetes Care, April 1, 2009; 32(4): 531 - 540. [Full Text] [PDF]

				J. Hopkins and M. Limacher The Role of Aspirin in Cardiovascular Disease Prevention in Women American Journal of Lifestyle Medicine, March 1, 2009; 3(2): 123 - 134. [Abstract] [PDF]

				F. Santilli, B. Rocca, R. De Cristofaro, S. Lattanzio, L. Pietrangelo, A. Habib, C. Pettinella, A. Recchiuti, E. Ferrante, G. Ciabattoni, et al. Platelet cyclooxygenase inhibition by low-dose aspirin is not reflected consistently by platelet function assays implications for aspirin "resistance". J. Am. Coll. Cardiol., February 24, 2009; 53(8): 667 - 677. [Abstract] [Full Text] [PDF]

				Y. Yano, T. Ohmori, S. Hoshide, S. Madoiwa, K. Yamamoto, T. Katsuki, T. Mitsuhashi, J. Mimuro, K. Shimada, K. Kario, et al. Determinants of thrombin generation, fibrinolytic activity, and endothelial dysfunction in patients on dual antiplatelet therapy: involvement of factors other than platelet aggregability in Virchow's triad Eur. Heart J., July 2, 2008; 29(14): 1729 - 1738. [Abstract] [Full Text] [PDF]

				B. S. Karon, A. Wockenfus, R. Scott, S. J. Hartman, J. P. McConnell, P. J. Santrach, and A. S. Jaffe Aspirin Responsiveness in Healthy Volunteers Measured with Multiple Assay Platforms Clin. Chem., June 1, 2008; 54(6): 1060 - 1065. [Abstract] [Full Text] [PDF]

				P.-S. Klein Comment on: DiChiara et al. (2007) The Effect of Aspirin Dosing on Platelet Function in Diabetic and Nondiabetic Patients: An Analysis From the Aspirin-Induced Platelet Effect (ASPECT) Study: Diabetes 56:3014-3019, 2007 Diabetes, May 1, 2008; 57(5): e10 - e10. [Full Text] [PDF]

				D. J. Kereiakes and P. A. Gurbel Peri-Procedural Platelet Function and Platelet Inhibition in Percutaneous Coronary Intervention J. Am. Coll. Cardiol. Intv., April 1, 2008; 1(2): 111 - 121. [Abstract] [Full Text] [PDF]

				P.-S. Klein Letter by Klein Regarding Article, "Evaluation of Dose-Related Effects of Aspirin on Platelet Function: Results From the Aspirin-Induced Platelet Effect (ASPECT) Study" Circulation, January 29, 2008; 117(4): e21 - e21. [Full Text] [PDF]

				P. A. Gurbel, K. P. Bliden, J. DiChiara, T. Gesheff, S. K. Chaganti, A. Etherington, U. S. Tantry, J. Newcomer, W. Weng, and N. K. Neerchal Response to the Letter Regarding Article, "Evaluation of Dose-Related Effects of Aspirin on Platelet Function: Results From the Aspirin-Induced Platelet Effect (ASPECT) Study" Circulation, January 29, 2008; 117(4): e22 - e22. [Full Text] [PDF]

				C. Gachet and B. Aleil Testing antiplatelet therapy Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A28 - A34. [Abstract] [Full Text] [PDF]

				P. A. Gurbel, R. C. Becker, K. G. Mann, S. R. Steinhubl, and A. D. Michelson Platelet Function Monitoring in Patients With Coronary Artery Disease J. Am. Coll. Cardiol., November 6, 2007; 50(19): 1822 - 1834. [Abstract] [Full Text] [PDF]