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4 years after withdrawal of rofecoxib: where do we stand today?

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Abstract

On the 24th of October 2006, the European Medicines Agency (EMEA) stated that “it cannot be excluded that non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) may be associated with a small increase in the absolute risk for thrombotic events”. Reviewing the most recent literature including meta-analyses of randomized clinical studies and pharmacoepidemiological studies show that this statement contrasts with the 2005 EMEA evaluation of cyclooxygenase-2 inhibitors, which contained a number of regulations including several contraindications for coxibs. Recent clinical data indicate that the entire substance group of NSAIDs may have cardiovascular side effects but to different degrees. Results of basic research support these observations showing that the increase for cardiovascular risk not only depends on the ratio of inhibition of thromboxan and prostacyclin but also on other mechanisms including blood pressure elevation and cyclooxygenase independent actions. In clinical practice, many patients require anti-inflammatory therapy with NSAIDs but are at high cardiovascular and gastrointestinal risk. The combination of nsNSAIDs with proton pump inhibitors shows comparable safety to coxibs in averting upper gastrointestinal events, but evidence is increasing coxibs have advantages regarding lower gastrointestinal side effects. Concomitant therapy with aspirin is another issue. There is a negative effect on gastrointestinal safety, as well as the influence of nsNSAIDs on the cardioprotective effect of aspirin. As the contraindications for coxibs announced by the EMEA may prevent some patients from receiving optimal treatment, a warning for the entire substance group, as issued by the American Food and Drug Administration, with no contraindictions, would certainly be more reasonable.

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  1. Department of Anaesthesiology and Intensive Care Medicine, Wilhelminenspital, der Stadt Wien, Montleartstrasse 37, 1160, Vienna, Austria

    W. Jaksch

  2. Department of Internal Medicine, Hospital of the Elisabethinen, Voelkermarkterstrasse 15-19, 9020, Klagenfurt, Austria

    C. Dejaco & M. Schirmer

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Jaksch, W., Dejaco, C. & Schirmer, M. 4 years after withdrawal of rofecoxib: where do we stand today?. Rheumatol Int 28, 1187–1195 (2008). https://doi.org/10.1007/s00296-008-0650-4

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