Selective COX-2 inhibitors and risk of myocardial infarction

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
myocardial 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 currently 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. Copyright (C) 2005 S. Karger
AG, Basel.