Selective inhibitors of
cyclooxygenase-2 (COX-2, 'coxibs') are highly effective anti-inflammatory and
analgesic drugs that exert their action by preventing the formation of
prostanoids. Recently some
coxibs, which were designed to exploit the advantageous effects of non-steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myo cardial
infarction and atherothrombotic events. This has led to the withdrawal of
rofecoxib from global markets, and warnings have been issued by
drug authorities about similar events during the use of
celecoxib or
valdecoxib/
parecoxib, bringing about questions of an inherent atherothrombotic risk of all
coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX-2 on the cardiovascular system. Although COX-2, in contrast to the
cyclooxygenase-1 (COX-1)
isoform, is regarded as an inducible
enzyme that only has a role in pathophysiological processes like
pain and
inflammation, experimental and clinical studies have shown that COX-2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX-2-dependent formation of
prostanoids not only results in the mediation of
pain or inflammatory signals but also in the maintenance of vascular integrity. Especially
prostacyclin (PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX-2, and its levels are reduced to less than half of normal when COX-2 is inhibited. This review outlines the rationale for the development of selective
COX-2 inhibitors and the pathophysiological consequences of selective inhibition of COX-2 with special regard to vasoactive
prostaglandins. It describes
coxibs that are current ly available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights.