Anti-inflammatories, Heart Attacks, and GI Bleeding

          This blog is based on an article that recently appeared in Lancet, vol. 382, pp779-789, Sept. 6, 2013. The article was a meta-analysis (and see my previous blogs on the problems inherent inj meta-analyses) of over 700 studies that looked at the relationship between anti-inflammatory drugs, heart attacks, and GI bleeding. (Recall that Vioxx was taken off the market because of an increase in heart attacks and strokes.)

     A little biochemistry is in order. There are two enzymes released by platelets that synthesize prostaglandins, called COX-1 and COX-2 for short. COX-2 prostaglandins mediate pain and inflammation, and COX-1 prostaglandins protect against GI bleeding, especially in the stomach. Aspirin blocks the production of both enzymes irreversibly, which is why aspirin is used to prevent strokes and reduce pain and inflammation,  and can cause GI bleeding. The studies looked at NSAIDs such as ibuprofen (Advil, Motrin), naproxen (Naprosen, Aleve), and diclofenac. These NSAIDS block both COX-1 and COX-2. The studies also looked at anti-inflammatory drugs such as Celebrex that only blocked COX-2,(called coxibs), and therefore did not increase the risk of GI bleeding.

     The study showed that all NSAIDs increased the risk for GI bleeding, but in no case were acid-blockers such as Prilosec and Prevacid used, which would have decreased the risk. The surprising result was that not only did coxibs increase the risk of heart attacks by one-third, but that all the NSAIDs except Aleve did as well, so that Aleve is the safest from a vascular point of view. Unfortunately, naproxen also had the highest risk of GI bleeding.

     Thus the safest anti-pain and anti-inflammatory drug would appear to be Aleve, but an acid-blocking drug should be taken with it to reduce the risk of GI bleeding.