Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Celecoxib Does Not Attenuate the Antiplatelet Effects of Aspirin and Clopidogrel in Healthy Volunteers

  • Lee, Won-Jae (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Suh, Jung-Won (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Yang, Han-Mo (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kwon, Dong-A (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Cho, Hyun-Ju (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kang, Hyun-Jae (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Hyo-Soo (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Oh, Byung-Hee (Department of Internal Medicine, Seoul National University College of Medicine)
  • Received : 2009.11.18
  • Accepted : 2009.12.14
  • Published : 2010.07.30
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Abstract

Background and Objectives: The prevalence of arthritis, which is often treated with celecoxib, is high in patients with coronary artery disease. Furthermore, celecoxib has been reported to reduce restenosis after coronary stenting by inhibiting expression of the proto-oncogene Akt. A concern is that celecoxib increases thrombogenicity by inhibiting the synthesis of prostacyclin in endothelial cells. However, it is not known whether the administration of celecoxib will attenuate the antiplatelet effects of aspirin and clopidogrel, which are used after stenting. We addressed this gap in our knowledge. Subjects and Methods: We recruited healthy volunteers (n=40) and randomized them into five subgroups (n=8 for each group: aspirin, celecoxib, aspirin+celecoxib, aspirin+clopidogrel, and aspirin+clopidogrel+celecoxib). Each subject received their medications for 6 days and blood samples were taken on day 0 and day 7. Celecoxib (200 mg twice a day), and/or aspirin (100 mg daily), and/or clopidogrel (75 mg daily) were administered. We compared platelet function among subgroups using light transmittance aggregometry and arachidonic acid metabolite assays. Results: Celecoxib treatment alone did not significantly affect platelet aggregation. The reduction in adenosine diphosphase (ADP)-induced platelet aggregation by aspirin+clopidogrel was not affected by addition of celecoxib (31.3${\pm}$6.9% vs. 32.4${\pm}$12.2%, p=0.83). Inhibition of collagen-induced platelet aggregation by aspirin+clopidogrel was not affected by addition of celecoxib (47.6${\pm}$13.4% vs. 51.6${\pm}$3.7%, p=0.69). Drug-induced changes in prostacyclin and thromboxane levels did not differ among treatment groups. Conclusion: Celecoxib treatment does not interfere with the antiplatelet effects of aspirin or clopidogrel, suggesting that celecoxib can be safely administered in combination with dual antiplatelet therapy in patients with coronary stenting without increased thrombogenicity.

Keywords

References

  1. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284: 1247-55. https://doi.org/10.1001/jama.284.10.1247
  2. Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946-52. https://doi.org/10.1056/NEJM200006293422603
  3. Koo BK, Kim YS, Park KW, et al. Effect of celecoxib on restenosis after coronary angioplasty with a Taxus stent (COREA-TAXUS trial): an open-label randomised controlled study. Lancet 2007;370:567-74. https://doi.org/10.1016/S0140-6736(07)61295-1
  4. Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005;352:1092-102. https://doi.org/10.1056/NEJMoa050493
  5. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1071-80. https://doi.org/10.1056/NEJMoa050405
  6. Fitzgerald GA. Coxibs and cardiovascular disease. N Engl J Med 2004; 351:1709-11. https://doi.org/10.1056/NEJMp048288
  7. Hawk E, Viner JL. The adenoma prevention with celecoxib and prevention of colorectal sporadic adenomatous polyps trials: stepping stones to progress. Cancer Epidemiol Biomarkers Prev 2007;16:185-7. https://doi.org/10.1158/1055-9965.EPI-06-1086
  8. ADAPT Research Group. Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT). PLoS Clin Trials 2006;1:e33. https://doi.org/10.1371/journal.pctr.0010033
  9. Chae SC. Antiplatelet agents in high-risk patients with coronary artery disease. Korean Circ J 2004;34:23-7. https://doi.org/10.4070/kcj.2004.34.1.23
  10. Kim SS, Jeong MH, Sim DS, et al. Very late thrombosis of a drug-eluting stent after discontinuation of dual antiplatelet therapy in a patient treated with both drug-eluting and bare-metal stents. Korean Circ J 2009;39:205-8. https://doi.org/10.4070/kcj.2009.39.5.205
  11. Park JC, Jeong MH, Kim JH, et al. Clinical characteristics of coronary interventions in old aged patients. Korean Circ J 1998;28:256-61. https://doi.org/10.4070/kcj.1998.28.2.256
  12. Fiorina P, Perseghin G, De Cobelli F, et al. Altered kidney graft highenergy phosphate metabolism in kidney-transplanted endstage renal disease type 1 diabetic patients: a cross-sectional analysis of the effect of kidney alone and kidney-pancreas transplantation. Diabetes Care 2007;30:597-603. https://doi.org/10.2337/dc06-1324
  13. McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX- 2. Proc Natl Acad Sci U S A 1999;96:272-7. https://doi.org/10.1073/pnas.96.1.272
  14. FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase- 2. N Engl J Med 2001;345:433-42. https://doi.org/10.1056/NEJM200108093450607
  15. Arrebola MM, De la Cruz JP, Villalobos MA, Pinacho A, Guerrero A, Sanchez de la Cuesta F. In vitro effects of clopidogrel on the plateletsubendothelium interaction, platelet thromboxane and endothelial prostacyclin production, and nitric oxide synthesis. J Cardiovasc Pharmacol 2004;43:74-82. https://doi.org/10.1097/00005344-200401000-00012
  16. Leese PT, Hubbard RC, Karim A, Isakson PC, Yu SS, Geis GS. Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: a randomized, controlled trial. J Clin Pharmacol 2000;40:124-32. https://doi.org/10.1177/00912700022008766
  17. Van Ryn J, Kink-Eiband M, Kuritsch I, et al. Meloxicam does not affect the antiplatelet effect of aspirin in healthy male and female volunteers. J Clin Pharmacol 2004;44:777-84. https://doi.org/10.1177/0091270004266623
  18. Wilner KD, Rushing M, Walden C, et al. Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers. J Clin Pharmacol 2002;42:1027-30.
  19. Renda G, Tacconelli S, Capone ML, et al. Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease. Clin Pharmacol Ther 2006;80:264-74. https://doi.org/10.1016/j.clpt.2006.05.004
  20. Yang HM, Kim HS, Park KW, et al. Celecoxib, a cyclooxygenase-2 inhibitor, reduces neointimal hyperplasia through inhibition of Akt signaling. Circulation 2004;110:301-8. https://doi.org/10.1161/01.CIR.0000135467.43430.16
  21. Wang K, Tarakji K, Zhou Z, et al. Celecoxib, a selective cyclooxygenase- 2 inhibitor, decreases monocyte chemoattractant protein1 expression and neointimal hyperplasia in the rabbit atherosclerotic balloon injury model. J Cardiovasc Pharmacol 2005;45:61-7. https://doi.org/10.1097/00005344-200501000-00011
  22. Steffel J, Hermann M, Greutert H, et al. Celecoxib decreases endothelial tissue factor expression through inhibition of c-Jun terminal NH2 kinase phosphorylation. Circulation 2005;111:1685-9. https://doi.org/10.1161/01.CIR.0000160358.63804.C9
  23. Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor? Blood 2003;102:449-61. https://doi.org/10.1182/blood-2002-12-3882
  24. Solomon SD, Wittes J, Finn PV, et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 2008;117:2104-13. https://doi.org/10.1161/CIRCULATIONAHA.108.764530
  25. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 2006;296: 1633-44. https://doi.org/10.1001/jama.296.13.jrv60011
  26. White WB, West CR, Borer JS, et al. Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol 2007;99:91-8. https://doi.org/10.1016/j.amjcard.2006.07.069
  27. Johnsen SP, Larsson H, Tarone RE, et al. Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study. Arch Intern Med 2005;165:978-84. https://doi.org/10.1001/archinte.165.9.978
  28. Belton O, Byrne D, Kearney D, Leahy A, Fitzgerald DJ. Cyclooxygenase- 1 and -2-dependent prostacyclin formation in patients with atherosclerosis. Circulation 2000;102:840-5. https://doi.org/10.1161/01.CIR.102.8.840
  29. Kobayashi T, Tahara Y, Matsumoto M, et al. Roles of thromboxane A(2) and prostacyclin in the development of atherosclerosis in apoEdeficient mice. J Clin Invest 2004;114:784-94. https://doi.org/10.1172/JCI200421446
  30. Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation 2005;112:759-70. https://doi.org/10.1161/CIRCULATIONAHA.105.568451

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