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J Am Coll Cardiol, 2003; 41:961-965, doi:10.1016/S0735-1097(02)03014-0
© 2003 by the American College of Cardiology Foundation
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CLINICAL STUDY: ANTIPLATELET THERAPY

A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease

Patricia A. Gum, MD*, Kandice Kottke-Marchant, MD, PhD*, Patricia A. Welsh*, Jennifer White, MS* and Eric J. Topol, MD, FACC*,*

* Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

Manuscript received May 6, 2002; revised manuscript received October 3, 2002, accepted November 11, 2002.

* Reprint requests and correspondence: Dr. Eric J. Topol, Department of Cardiovascular Medicine, Desk F25, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
topole{at}ccf.org

OBJECTIVES: This study was designed to determine if aspirin resistance is associated with clinical events.

BACKGROUND: Aspirin resistance, defined by platelet function testing and presumed clinical unresponsiveness to aspirin, has been previously reported by our group and others. However, little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events.

METHODS: We prospectively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin (325 mg/day for ≥7 days) and no other antiplatelet agents. We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate (ADP) and arachidonic acid (AA). The primary outcome was the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA). Mean follow-up was 679 ± 185 days. Aspirin resistance was defined as a mean aggregation of ≥70% with 10 µM ADP and ≥20% with 0.5 mg/ml AA.

RESULTS: Of the patients studied, 17 (5.2%) were aspirin resistant and 309 (94.8%) were not aspirin resistant. During follow-up, aspirin resistance was associated with an increased risk of death, MI, or CVA compared with patients who were aspirin sensitive (24% vs. 10%, hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.10 to 8.90, p = 0.03). Stratified multivariate analyses identified platelet count, age, heart failure, and aspirin resistance to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 4.14, 95% CI 1.42 to 12.06, p = 0.009).

CONCLUSIONS: This study demonstrates the natural history of aspirin resistance in a stable population, documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance.

Abbreviations and Acronyms
  AA
  arachidonic acid
  ADP
  adenosine diphosphate
  CI
  confidence interval
  CVA
  cerebrovascular accident
  HR
  hazard ratio
  MI
  myocardial infarction




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J. Am. Coll. Cardiol., December 13, 2005; (2005) j.jacc.2005.08.058v1.
[Abstract] [Full Text] [PDF]

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P. A. Gurbel, K. P. Bliden, W. Samara, J. A. Yoho, K. Hayes, M. Z. Fissha, and U. S. Tantry
Clopidogrel Effect on Platelet REactivity in Patients With Stent Thrombosis: Results of the CREST Study
J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1827 - 1832.
[Abstract] [Full Text] [PDF]

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U. S. Tantry, K. P. Bliden, and P. A. Gurbel
Overestimation of Platelet Aspirin Resistance Detection by Thrombelastograph Platelet Mapping and Validation by Conventional Aggregometry Using Arachidonic Acid Stimulation
J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1705 - 1709.
[Abstract] [Full Text] [PDF]

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A. O. Maree, R. J. Curtin, M. Dooley, R. M. Conroy, P. Crean, D. Cox, and D. J. Fitzgerald
Platelet Response to Low-Dose Enteric-Coated Aspirin in Patients With Stable Cardiovascular Disease
J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1258 - 1263.
[Abstract] [Full Text] [PDF]

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 Annals of Clinical & Laboratory ScienceHome page
E. Fosslien
Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs
Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 347 - 385.
[Abstract] [Full Text] [PDF]

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P. J. Mason, A. K. Jacobs, and J. E. Freedman
Aspirin Resistance and Atherothrombotic Disease
J. Am. Coll. Cardiol., September 20, 2005; 46(6): 986 - 993.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, C. Ramirez, M. Sabate, P. Jimenez-Quevedo, R. Hernandez, R. Moreno, J. Escaned, F. Alfonso, et al.
Platelet Function Profiles in Patients With Type 2 Diabetes and Coronary Artery Disease on Combined Aspirin and Clopidogrel Treatment
Diabetes, August 1, 2005; 54(8): 2430 - 2435.
[Abstract] [Full Text] [PDF]

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J. J. Saseen
ASHP Therapeutic Position Statement on the Daily Use of Aspirin for Preventing Cardiovascular Events
Am. J. Health Syst. Pharm., July 1, 2005; 62(13): 1398 - 1405.
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H Mani, B Luxembourg, C Klaffling, M Erbe, and E Lindhoff-Last
Use of native or platelet count adjusted platelet rich plasma for platelet aggregation measurements
J. Clin. Pathol., July 1, 2005; 58(7): 747 - 750.
[Abstract] [Full Text] [PDF]

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P. Wenaweser, J. Dorffler-Melly, K. Imboden, S. Windecker, M. Togni, B. Meier, A. Haeberli, and O. M. Hess
Stent Thrombosis Is Associated With an Impaired Response to Antiplatelet Therapy
J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1748 - 1752.
[Abstract] [Full Text] [PDF]

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S. R. Steinhubl, R. Charnigo, and D. J. Moliterno
Resistance to Antiplatelet Resistance: Is it Justified?
J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1757 - 1758.
[Full Text] [PDF]

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 Eur Heart JHome page
P. Wenaweser, C. Rey, F. R. Eberli, M. Togni, D. Tuller, S. Locher, A. Remondino, C. Seiler, O. M. Hess, B. Meier, et al.
Stent thrombosis following bare-metal stent implantation: success of emergency percutaneous coronary intervention and predictors of adverse outcome
Eur. Heart J., June 2, 2005; 26(12): 1180 - 1187.
[Abstract] [Full Text] [PDF]

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 The Annals of PharmacotherapyHome page
E. Papp, V. Havasi, J. Bene, K. Komlosi, L. Czopf, E. Magyar, C. Feher, G. Feher, B. Horvath, Z. Marton, et al.
Glycoprotein IIIA Gene (PlA) Polymorphism and Aspirin Resistance: Is There Any Correlation?
Ann. Pharmacother., June 1, 2005; 39(6): 1013 - 1018.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
E. R. Bates and W. C. Lau
Controversies in Antiplatelet Therapy for Patients With Cardiovascular Disease
Circulation, May 3, 2005; 111(17): e267 - e271.
[Full Text] [PDF]

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 StrokeHome page
P. Harrison, H. Segal, K. Blasbery, C. Furtado, L. Silver, and P. M. Rothwell
Screening for Aspirin Responsiveness After Transient Ischemic Attack and Stroke: Comparison of 2 Point-of-Care Platelet Function Tests With Optical Aggregometry
Stroke, May 1, 2005; 36(5): 1001 - 1005.
[Abstract] [Full Text] [PDF]

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 CLIN APPL THROMB HEMOSTHome page
J. Mikkelsson, M. Perola, and P. J. Karhunen
Genetics of Platelet Glycoprotein Receptors: Risk of Thrombotic Events and Pharmacogenetic Implications
Clinical and Applied Thrombosis/Hemostasis, April 1, 2005; 11(2): 113 - 125.
[Abstract] [PDF]

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A. T.L. Ong, A. Hoye, J. Aoki, C. A.G. van Mieghem, G. A. Rodriguez Granillo, K. Sonnenschein, E. Regar, E. P. McFadden, G. Sianos, W. J. van der Giessen, et al.
Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation
J. Am. Coll. Cardiol., March 15, 2005; 45(6): 947 - 953.
[Abstract] [Full Text] [PDF]

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 ANN INTERN MEDHome page
S. Sanderson, J. Emery, T. Baglin, and A.-L. Kinmonth
Narrative Review: Aspirin Resistance and Its Clinical Implications
Ann Intern Med, March 1, 2005; 142(5): 370 - 380.
[Abstract] [Full Text] [PDF]

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V. L. Serebruany, S. R. Steinhubl, P. B. Berger, A. I. Malinin, D. L. Bhatt, and E. J. Topol
Variability in platelet responsiveness to clopidogrel among 544 individuals
J. Am. Coll. Cardiol., January 18, 2005; 45(2): 246 - 251.
[Abstract] [Full Text] [PDF]

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A. D. Michelson
Platelet Function Testing in Cardiovascular Diseases
Circulation, November 9, 2004; 110(19): e489 - e493.
[Full Text] [PDF]

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 Eur Heart JHome page
D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, C. Ramirez, M. Sabate, C. Banuelos, R. Hernandez-Antolin, J. Escaned, R. Moreno, F. Alfonso, et al.
High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability
Eur. Heart J., November 1, 2004; 25(21): 1903 - 1910.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
M. Cattaneo
Aspirin and Clopidogrel: Efficacy, Safety, and the Issue of Drug Resistance
Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1980 - 1987.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
S. P. Schulman
Antiplatelet Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes
JAMA, October 20, 2004; 292(15): 1875 - 1882.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
J. F. Toole, D. C. Sane, and K. Bettermann
Stroke Prevention: Optimizing the Response to a Common Threat
JAMA, October 20, 2004; 292(15): 1885 - 1887.
[Full Text] [PDF]

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 CirculationHome page
J.P. Collet, G. Montalescot, B. Blanchet, M.L. Tanguy, J.L. Golmard, R. Choussat, F. Beygui, L. Payot, N. Vignolles, J.P. Metzger, et al.
Impact of Prior Use or Recent Withdrawal of Oral Antiplatelet Agents on Acute Coronary Syndromes
Circulation, October 19, 2004; 110(16): 2361 - 2367.
[Abstract] [Full Text] [PDF]

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 Journal of Pharmacy PracticeHome page
B. S. Wiggins and S. Spinler
Antiplatelet and Antithrombin Therapy for Early Management of Acute Coronary Syndromes
Journal of Pharmacy Practice, October 1, 2004; 17(5): 347 - 369.
[Abstract] [PDF]

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 ChestHome page
C. Patrono, B. Coller, G. A. FitzGerald, J. Hirsh, and G. Roth
Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest, September 1, 2004; 126(3_suppl): 234S - 264S.
[Abstract] [Full Text] [PDF]


 
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