NSAIDs and COX2 inhibitors

A great, albeit technical, article on the relative risks and benefits of NSAIDs and Cox 2 inhibitors in this months Journal of Clinical Investigation. NSAIDS, such as ibuprofen, naproxen, aspirin inhibit both cyclooxygenase (COX) 1 and 2, although to different extents. Low-dose aspirin preferentially blocks COX2 accounting for much of its cardioprotective effects. COX1 is widely expressed while COX2 is involved primarily in inflammation. COX2 inhibitors were designed to block inflammation (and pain) in those who couldn't tolerate traditional NSAIDS

Some interesting highlights

1. Several "traditional" NSAIDS such as diclofenac and meloxicam are fairly COX2 specific, with diclofenac (marketed as Voltaren) comprable to celecoxib (Celebrex) in both the test tube and actual side effect profile of patients taking it.

2. Naproxen may have some protective effect on cardiovascular disease because of its long half-life and relative specificity for COX1

3. Long term use is probably very important in raising the risk of both traditional NSAIDs and COX2 inhibitors. So use for a few days with an acute injury is probably insignficant for an indivdual

4. More than causing heart disease themselves, COX2 inhibitors block the ability to respond to a stimuli that causes thrombosis (clotting of blood which is the acute trigger of most heart attacks and strokes). Mice that have a defect that mimics the effect of COX2 inhibition don't get spontaneous clots, but are at increased risk when manipulated to cause clotting. Similarly, the greatest risks of COX2 inhibitors in trials were seen in patients with underlying causes of clotting (those undergoing coronary artery bypass or with rheumatoid arthirits)

The article also gives a good history of how the problems with COX2 inhibitors were worked out.