Understanding the NSAID related risk of vascular eventsBMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7546.895 (Published 13 April 2006) Cite this as: BMJ 2006;332:895
- Harald E Vonkeman, rheumatologist (H.Vonkeman@ziekenhuis-mst.nl)1,
- Jacobus R B J Brouwers, professor of pharmacotherapeutics2,
- Mart A F J van de Laar, professor of rheumatology1
- 1 Department of Rheumatology and Clinical Immunology, Medisch Spectrum Twente Hospital and University of Twente, Enschede, Netherlands
- 2 Groningen University Institute for Drug Exploration and Groningen Research Institute of Pharmacy, Department of Social Pharmacy, Pharmacoepidemiology and Pharmacotherapy, Groningen, Netherlands
- Correspondence to: H E Vonkeman
- Accepted 8 February 2006
Concern is growing about an increased risk of thrombotic events (including myocardial infarction and stroke) during the use of non-steroidal anti-inflammatory drugs (NSAIDs), in particular the so called selective cyclo-oxygenase-2 (COX 2) inhibitors. Although clinical trials give conflicting results with respect to the incidence of vascular events, increasing evidence shows that a class effect might exist for selective COX 2 inhibitors. Even before the massive introduction of selective COX 2 inhibitors, observational studies showed that the use of NSAIDs causes congestive heart failure in elderly patients.1 2 Conversely, the discontinuation of NSAIDs has also been associated with increased risk of myocardial infarction, especially in the first several weeks after stopping chronic NSAID treatment.3
Many different mechanisms could explain the different effects of classic NSAIDs and selective COX 2 inhibitors in relation to thrombotic vascular events. In this review we link biochemical facts concerning NSAIDs and COX inhibitors with data from clinical trials.
Key enzymes: COX 1 and COX 2
The key step in the synthesis of prostaglandins, the transformation of arachidonic acid to prostaglandin H2, is catalysed by two different isoenzymes—cyclo-oxygenase-1 and cyclo-oxygenase-2.4 COX 1 is expressed constitutively at variable concentrations and regulates normal physiology, such as the maintenance of gastric mucosal integrity, kidney function, and platelet aggregation. Conversely, COX 2 is usually undetectable in most tissues and is selectively expressed after exposition to inflammatory mediators or trauma (fig 1).
The hypothesis formed is that the adverse gastrointestinal effects of NSAIDs are attributable to the inhibition of COX 1 and that selective inhibition of COX 2 would …