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Narrative Review

Vol. 8 No. 2 (2005)

The Fall of Titans: The Need to Reassess COX-2 Inhibitors

  • Steven Lin, BMSc
November 8, 2020




  1. Health Canada. Statistics Canada microdata tape Canadian Community Health Survey, 2000. Available at: http://www.phac Accessibility verified April 17, 2005.
  2. Intercontinental Medical Statistics Canada. 1999. Available at: Accessibility verified April 17, 2005.
  3. Intercontinental Medical Statistics Canada. 2003. Available at: Accessibility verified April 17, 2005.
  4. Luong C, Miller A, Barnett J, et al. The structure of human cyclooxygenase-2; conservation and flexibility of the NSAID binding site. Nat Struct Biol 3:927-33; 1996.
  5. Hawkey CJ. COX-2 inhibitors. Lancet 353(9149):307-14; 1999.
  6. Gierse JK, McDonald JJ, Hauser SD, et al. A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors. J Biol Chem 271:15810-4; 1996.
  7. Chandrasekharan NV, Dai H, Roos KL, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A 99(21):13926-31; 2002.
  8. Henry D, Lim LL, Garcia Rodriguez LA, et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative metaanalysis. BMJ 312(7046):1563-6; 1996.
  9. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 343:1520-8; 2000.
  10. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 286:954-9; 2001.
  11. Food and Drug Administration Advisory Committee. Cardiovascular Safety Review of Rofecoxib. 2001. Available at: Accessibility verified April 17, 2005.
  12. FitzGerald GA. Coxibs and Cardiovascular Disease. N Engl J Med 351:1709-11; 2004.
  13. Sibbald B. Rofecoxib (Vioxx) voluntarily withdrawn from market. CMAJ 171(9):1027-8; 2004.
  14. Canadian Broadcasting Corporation. 2004. Available at: Accessibility verified April 17, 2005.
  15. 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 284(10):1247-55; 2000.
  16. Lu HL. Statistical Reviewer Briefing Document for the Advisory Committee. Available at: Accessibility verified April 17, 2005.
  17. FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 345(6):433-42; 2001.
  18. Warner TD, Giuliano F, Vojnovic I, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A 96:7563-8; 1999.
  19. Couzin J. Clinical trials. Halt of Celebrex study threatens drug's future, other trials. Science 306(5705):2170; 2004.
  20. Topol EJ. Arthritis medicines and cardiovascular events--"house of coxibs". JAMA 293(3):366-8; 2005.
  21. Caughey GE, Cleland LG, Penglis PS, et al. Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2. J Immunol 167(5):2831-8; 2001.
  22. Dancu MB, Berardi DE, Vanden Heuvel JP, et al. Asynchronous shear stress and circumferential strain reduces endothelial NO synthase and cyclooxygenase-2 but induces endothelin-1 gene expression in endothelial cells. Arterioscler Thromb Vasc Biol 24(11):2088-94; 2004.
  23. Warner TD, Vojnovic I, Giuliano F, et al. Cyclooxygenases 1, 2, and 3 and the production of prostaglandin I2: investigating the activities of acetaminophen and cyclooxygenase-2-selective inhibitors in rat tissues. J Pharmacol Exp Ther 310(2):642-7; 2004.
  24. Ott E, Nussmeier NA, Duke PC, et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 125:1481-92; 2003.
  25. Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 352(11):1081-91; 2005.
  26. Food and Drug Administration. Alert for Healthcare Professionals Valdecoxib (marketed as Bextra), 2005. Available at: valdecoxibHCP.htm. Accessibility verified April 17, 2005.
  27. Sibbald B. Pfizer to withdraw valdecoxib (Bextra) at Health Canada's request. CMAJ 172(10):e1298; 2005.


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