[What is new about nonsteroidal antiinflamatory drugs?]

NSAIDs contain nonselective cyclooksygenase inhibitors (for COX-1 and COX-2), inhibitors to the preferential COX-2, the coxibs (sulphonamides, methylsulphones, phenylacethic acid derivatives) with 1000 fold selectivities for COX-2. COX-2 enzyme isoform are constitutively expressed in normal gastric tissue in animals and humans, in the cardiovascular system, renal, central nervous system and other. COX-2 is involved in the ischemic preconditioning mechanism and sulphones have a prooxidant activity. COX-2 inhibitors increased risk for thrombotic cardiovascular events. Long-term study VIGOR, CLASS, TARGET MEDAL revealed that celecoxib, rofecoxib, lumiracoxib, etoricoxib significantly reduced the risk of major gastrointestinal effects (ulcers, perforations, bleeding) than nonselective NSAIDs, but the rates of complicated upper gastrointestinal events were similar for etoricoxib and diclofenac. Only in VIGOR trial incidence of cardiovascular events was greater. No evidence that concomitant ASA reduced risk for cardivascular events. Potential differences in cardiovascular outcomes with the selective COX-2 inhibitors may be due to differences in the drugs molecular structures, pharmacokinetics and pharmacodynamics. In the "prothrombotic environment" contribution disorders in the balance between thromboxan A2 and prostacyclin, increased aggregation plaque, hypertension, endothelial cell dysfunction, impaired angiogenesis. Moreover COX-2 may plays a crucial role in atherosclerotic plaque stability or instability. The cardiovascular risk may be dose related and depends on duration therapy, variable selectivity for COX-2.