Abstract
The dramatic withdrawal of rofecoxib on 30 September 2004, along with safety concerns about other cyclo-oxygenase (COX)-2 inhibitors (especially valdecoxib), raises important issues for clinicians, pharmaceutical companies and regulatory authorities. Some of these are examined in this article, including: (i) was the cardiotoxicity of rofecoxib evident long before its withdrawal?; (ii) is the thrombotic hazard a class effect that is applicable to all COX-2 inhibitors?; (iii) may conventional NSAIDs also confer a risk of cardiovascular thrombosis?; and (iv) is there any future for selective COX-2 inhibitors?
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References
Vioxx: an unequal partnership between safety and efficacy. Lancet 2004; 364: 1287–8
Langton PE, Hankey GJ, Eikelboom JW. Cardiovascular safety of rofecoxib (Vioxx): lessons learned and unanswered questions. Med J Aust 2004; 181: 524–5
Dieppe PA, Ebrahim S, Martin RM, et al. Lessons from the withdrawal of rofecoxib. BMJ 2004; 329: 867–8
Topol EJ. Failing the public health: Rofecoxib, Merck, and the FDA. N Engl J Med 2004; 351: 1707–9
FitzGerald GA. Coxibs and cardiovascular disease. N Engl J Med 2004; 351: 1709–11
Horton R. Vioxx, the implosion of Merck, and aftershocks at the FDA. Lancet 2004; 364: 1995–6
Clark DWJ, Layton D, Shakir SAW. Do some inhibitors of COX-2 increase the risk of thromboembolic events? Linking pharmacology with pharmacoepidemiology. Drug Saf 2004; 27: 427–56
Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001; 286: 954–9
FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345: 433–42
Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003; 348: 891–9
Mukherjee D. Selective cyclooxygenase-2 (COX-2) inhibitors and potential risk of cardiovascular events. Biochem Pharmacol 2002; 63: 817–21
Solomon DH, Schneeweiss S, Glynn RJ, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004; 109: 2068–73
Campen DH, Graham D, Cheetham C, et al. Risk of acute cardiac events among patients treated with cyclooxygenase-2 selective and non-selective-nonsteroidal antiinflammatory drugs [abstract 1756]. Arthritis Rheum 2004; 50(9 Suppl.): S657
Meagher EA. Balancing gastroprotection and cardioprotection with selective cyclo-oxygenase-2 inhibitors: clinical implications. Drug Saf 2003; 26: 913–24
Jüni P, Nartey L, Reichenbach S, et al. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004; 364: 2021–9
Lipsky PE, Brooks P, Crofford LJ, et al. Unresolved issues in the role of cyclooxygenase-2 in normal physiologic processes and disease. Arch Intern Med 2000; 160: 913–20
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 2003; 125: 1481–92
FitzGerald G, Furberg C, Psaty B. Invited lecture at the American Heart Association Scientific Sessions 2004 [online]. Available from URL: http://www.jointandbone.org [Accessed 2005 Feb 3]
Jüni P, Rutjes AWS, Dieppe PA. Are selective COX-2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? BMJ 2002; 324: 1287–8
Topol EJ, Falk GW. A coxib a day won’t keep the doctor away. Lancet 2004; 364: 639–40
Cyclo-Oxygenase - 2 Inhibitors. WHO pharmaceuticals newsletter, 2004; 5: 7-8 [online]. Available from URL: http://www.who.int/medicines/library/pnewslet/5news2004.pdf [Accessed 2005 Feb 16]
Topol EJ. Arthritis medicines and cardiovascular events: ‘house of coxibs’. JAMA 2005; 293: 366–8
Day R. Hypertension in the patients with arthritis: have we been underestimating its significance. J Rheumatol 2003; 30: 642–5
Singh G, Miller JD, Huse DM, et al. Consequences of increased systolic blood pressure in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol 2003; 30: 714–9
Ray WA, Griffin MR, Stein CM. Cardiovascular toxicity of valdecoxib. N Engl J Med 2004; 351: 2767
Bannwarth B, Berenbaum F. Clinical pharmacology of lumiracoxib, a second generation COX-2 selective inhibitor. Exp Opin Invest Drugs. In press
Fiorucci S, Antonnelli E, Burgaud JL, et al. Nitric oxide-releasing NSAIDs. A review of their current status. Drug Saf 2001; 24: 801–11
Wallace JL, Del Soldato P. The therapeutic potential of NONSAIDs. Fundam Clin Pharmacol 2003; 17: 11–20
Bannwarth B. Is licofelone, a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase, a promising alternative in anti-inflammatory therapy? Fundam Clin Pharmacol 2004; 18: 125–30
Day RO, Quinn DI, Conaghan PG, et al. Adverse drug reactions and their measurement in the rheumatic diseases. J Rheumatol 1995; 22: 983–8
Lasser KE, Allen PD, Woolhandler SJ, et al. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002; 287: 2215–20
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No sources of funding were used to assist in the preparation of this article. The author has attended Merck sponsored symposia as an invited speaker and was involved in clinical studies sponsored by Merck.
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Bannwarth, B. Do Selective Cyclo-Oxygenase-2 Inhibitors Have a Future?. Drug-Safety 28, 183–189 (2005). https://doi.org/10.2165/00002018-200528030-00001
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DOI: https://doi.org/10.2165/00002018-200528030-00001