Circulation. 2002;105:1650-1655
Published online before print March 25, 2002, doi: 10.1161/01.CIR.0000013777.21160.07
Published online before print March 25, 2002, doi: 10.1161/01.CIR.0000013777.21160.07
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(Circulation. 2002;105:1650.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events
From the Department of Medicine, University of Western Australia, Thrombosis and Haemophilia Unit, Royal Perth Hospital, Perth, Australia (J.W.E.); Hamilton Civic Hospitals Research Centre, Hamilton, Canada (J.H., J.I.W.); the Department of Medicine, McMaster University, Hamilton, Canada (J.H., J.I.W., S.Y.); Hemostasis Reference Laboratory, Hamilton Civic Hospitals, Hamilton, Canada (M.J.); the Biostatistics Department, Princess Margaret Hospital, Toronto, Canada (Q.Y.); and Population Health Institute, McMaster University, Hamilton, Canada (S.Y.).
Correspondence to Dr John Eikelboom, Thrombosis and Haemophilia Unit, Royal Perth Hospital, Wellington Street, Perth Box X2213 GPO, Perth WA 6897, Australia. E-mail john.eikelboom{at}health.wa.gov.au
Background— We studied whether aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population.
Methods and Results— Baseline urine samples were obtained from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Using a nested case-control design, we measured urinary 11-dehydro thromboxane B2 levels, a marker of in vivo thromboxane generation, in 488 cases treated with aspirin who had myocardial infarction, stroke, or cardiovascular death during 5 years of follow-up and in 488 sex- and age-matched control subjects also receiving aspirin who did not have an event. After adjustment for baseline differences, the odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of 11-dehydro thromboxane B2, with patients in the upper quartile having a 1.8-times-higher risk than those in the lower quartile (OR, 1.8; 95% CI, 1.2 to 2.7; P=0.009). Those in the upper quartile had a 2-times-higher risk of myocardial infarction (OR, 2.0; 95% CI, 1.2 to 3.4; P=0.006) and a 3.5-times-higher risk of cardiovascular death (OR, 3.5; 95% CI, 1.7 to 7.4; P<0.001) than those in the lower quartile.
Conclusions— In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity.
Key Words: aspirin • thromboxane • atherosclerosis • myocardial infarction • stroke
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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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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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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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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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R. Gonzalez-Conejero, J. Rivera, J. Corral, C. Acuna, J. A. Guerrero, and V. Vicente Biological Assessment of Aspirin Efficacy on Healthy Individuals: Heterogeneous Response or Aspirin Failure? Stroke, February 1, 2005; 36(2): 276 - 280. [Abstract] [Full Text] [PDF]
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S. Fries and T. Grosser The Cardiovascular Pharmacology of COX-2 Inhibition Hematology, January 1, 2005; 2005(1): 445 - 451. [Abstract] [Full Text] [PDF]
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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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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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C. H. Hennekens, K. Schror, S. Weisman, and G. A. FitzGerald Terms and Conditions: Semantic Complexity and Aspirin Resistance Circulation, September 21, 2004; 110(12): 1706 - 1708. [Full Text] [PDF]
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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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S. Fiorucci, A. Mencarelli, A. Meneguzzi, A. Lechi, B. Renga, P. del Soldato, A. Morelli, and P. Minuz Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans J. Am. Coll. Cardiol., August 4, 2004; 44(3): 635 - 641. [Abstract] [Full Text] [PDF]
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K. A. Tanaka, F. Szlam, N. Katori, A. Tsuda, and J. H. Levy In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery Br. J. Anaesth., August 1, 2004; 93(2): 257 - 262. [Abstract] [Full Text] [PDF]
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B. Schieffer, C. Bunte, J. Witte, K. Hoeper, R. H. Boger, E. Schwedhelm, and H. Drexler Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease J. Am. Coll. Cardiol., July 21, 2004; 44(2): 362 - 368. [Abstract] [Full Text] [PDF]
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J. van Ryn, M. Kink-Eiband, I. Kuritsch, U. Feifel, G. Hanft, G. Wallenstein, G. Trummlitz, and M. Pairet Meloxicam Does Not Affect the Antiplatelet Effect of Aspirin in Healthy Male and Female Volunteers J. Clin. Pharmacol., July 1, 2004; 44(7): 777 - 784. [Abstract] [Full Text] [PDF]
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S. D. Wiviott and E. M. Antman Clopidogrel Resistance: A New Chapter in a Fast-Moving Story Circulation, June 29, 2004; 109(25): 3064 - 3067. [Full Text] [PDF]
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F. Cipollone, E. Toniato, S. Martinotti, M. Fazia, A. Iezzi, C. Cuccurullo, B. Pini, S. Ursi, G. Vitullo, M. Averna, et al. A Polymorphism in the Cyclooxygenase 2 Gene as an Inherited Protective Factor Against Myocardial Infarction and Stroke JAMA, May 12, 2004; 291(18): 2221 - 2228. [Abstract] [Full Text] [PDF]
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J.-M. Dogne, J. Hanson, X. de Leval, P. Kolh, V. Tchana-Sato, L. de Leval, S. Rolin, A. Ghuysen, P. Segers, B. Lambermont, et al. Pharmacological Characterization of N-tert-Butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A2 Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 498 - 505. [Abstract] [Full Text] [PDF]
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