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The coxib story: some lessons and more questions

  • Robert M. Califf
    Correspondence
    Address for reprints: Robert M. Califf, MD, Duke Clinical Research Institute, PO Box 17969, Durham, North Carolina 27715, USA.
    Affiliations
    Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina USA
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      The clinical development of the “coxibs,” which specifically inhibit the cyclooxygenase (COX-2) pathway, represents a major triumph of biomedical science. Science based on fundamental discoveries unraveled the complex cyclooxygenase system. COX-1, a constituent of vessel walls and multiple other organ tissues, plays critical roles in regulating vascular tone and gut mucosal integrity.
      • FitzGerald G.A.
      • Patrono C.
      The coxibs, selective inhibitors of cyclooxygenase-2.
      In contrast, COX-2, which is induced by inflammation, mediates a significant component of the inflammatory response to various stimuli. As predicted from biologic experiments and animal models, specific blockade of the COX-2 system has a therapeutic anti-inflammatory effect associated with less gastrointestinal bleeding than nonspecific COX blockade.
      The VIGOR Study Group
      Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.
      These appealing clinical results have led to >36 million prescriptions being prescribed for COX-2 inhibitors during one 12-month period in the US alone.
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