Prevention of nonsteroidal anti-inflammatory drug-induced ulcer: looking to the future.

The great challenge for those attempting to develop safer NSAIDs is shifting from a focus on GI toxicity to the increasingly more appreciated cardiovascular toxicity. At present, coxib shows an unmatched GI safety and appears to be a rational choice for patients at a low cardiovascular risk who have had serious GI events. In these patients, however, a cost-effective alternative is the use of tNSAIDs associated with comedication with a low-cost PPI or PN400. Because it seems prudent to avoid coxibs in patients who have cardiovascular disease or who are at risk for it, naproxcinod will be an appealing alternative to coxibs and tNSAIDs. However, because naproxcinod carries a significant risk of GI bleeding, a comedication therapy with a PPI inhibitor will be required if these patients also present risk factors for GI events. Although the development of H2S-releasing anti-inflammatory drugs is in its infancy, the preclinical data available thus far provide cause for optimism. The quest for the development of NSAIDs devoid of cardiovascular toxicity and that spare the gastric mucosa to the same extent as that of a coxib, however, is still open.