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  • Review Article
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Drug Insight: cyclo-oxygenase-2 inhibitors—a critical appraisal

Nature Clinical Practice Rheumatology volume 3, pages 552–560 (2007)Cite this article

Abstract

Following the withdrawal of rofecoxib and valdecoxib, the discussion concerning selective cyclo-oxygenase (COX)-2 inhibitors was often characterized more by emotions than scientific evidence. In fact, the original rationale of these substances is still valid, in that selective COX2 inhibitors cause significantly fewer severe side effects in the gastrointestinal tract than traditional NSAIDs. Off-label long-term use of COX2 inhibitors in patients with a history of colorectal adenomas in well-designed, placebo-controlled trials showed that treatment with these agents is associated with an increased rate of cardiovascular adverse effects. Other studies have shown that both COX2 inhibitors and NSAIDs are associated with a similar cardiovascular risk, suggesting that there is presently no rationale for a further differentiation of these groups of drugs in terms of cardiovascular toxicity. Referring to the current debate, potential mechanisms underlying cardiovascular adverse effects associated with the long-term use of COX2 inhibitors and NSAIDs are discussed. Moreover, this Review summarizes the pharmacology of COX2 inhibitors with emphasis on their different pharmacokinetic characteristics.

Key Points

  • Cyclo-oxygenase (COX)-2 inhibitors significantly reduce gastrointestinal adverse effects associated with long-term use of traditional NSAIDs

  • COX2 inhibitors and NSAIDs are associated with a similar cardiovascular risk

  • In some individuals high-dose naproxen (500 mg twice daily) might have a neutral effect or confer a small cardioprotection by virtue of a >95% COX1 inhibition

  • Permanent blockade of COX2-dependent prostaglandins (i.e. cardiorenal hypothesis) rather then an imbalance between COX1-derived and COX2-derived prostanoids is the currently most plausible explanation for the cardiovascular hazard conferred by COX2 inhibitors and NSAIDs

  • Despite newly defined contraindications and warnings, COX2 inhibitors and NSAIDs still remain important tools in pain therapy

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Authors and Affiliations

  1. B Hinz is Full Professor of Toxicology and Pharmacology, and Head of the Institute of Toxicology and Pharmacology of the University of Rostock, Germany.,

    Burkhard Hinz

  2. both in the Department of Experimental and Clinical Pharmacology and Toxicology at the University of Erlangen, B Renner is a group leader and K Brune is Full Professor of Pharmacology and Toxicology, and Doerenkamp-Professor for Innovations in Animal and Consumer Protection, Germany.,

    Bertold Renner & Kay Brune

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  1. Burkhard Hinz
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Correspondence to Burkhard Hinz.

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Competing interests

Dr. Hinz has received consulting fees or honoraria from AstraZeneca and Novartis, and has received research support from Bayer. Dr. Renner has received research support from Merck Sharp & Dohme Limited, GlaxoSmithKline and Philip Morris USA. Dr. Brune has received consulting fees or honoraria from Bayer, Merck Sharp & Dohme Limited, and Novartis, and has received research support from Aventis, Bayer, Merck Sharp & Dohme Limited and Novartis.

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Hinz, B., Renner, B. & Brune, K. Drug Insight: cyclo-oxygenase-2 inhibitors—a critical appraisal. Nat Rev Rheumatol 3, 552–560 (2007). https://doi.org/10.1038/ncprheum0619

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