On the basis of their reduced potential to cause injury to the gastroduoden
al mucosa, cyclo-oxygenase (COX)-2-selective inhibitors were developed and
marketed as a safer alternative to traditional nonsteroidal anti-inflammato
ry drugs (NSAIDs). This manuscript reviews the major steps leading to the i
ntroduction of COX-2-selective inhibitors into clinical practice, from the
identification of the COX isoenzymes to their various roles in physiologica
l and pathological processes. The available data show that COX-2 inhibitors
have a favourable safety profile and are at least as effective as traditio
nal NSAIDs for the treatment of pain and inflammatory conditions with a red
uced incidence of gastrointestinal complications. Emerging evidence points
to new and unanticipated effects from these agents. COX-2 inhibition appear
s to play an important role in the modulation of intestinal polyposis and c
olorectal carcinogenesis. Additionally, COX-2 expression may be associated
with inflammatory responses leading to the occurrence of Alzheimer's diseas
e and potentially, COX-2 inhibitors could be used to retard the progression
of this condition. However, by decreasing prostacyclin production, COX-2 i
nhibitors may lead to increased prothrombotic activity and increase the ris
k of cardiovascular events. Until further large-scale prospective studies a
re performed, and the magnitude of these potential risks is quantified, COX
-2 inhibitors should be used with caution in patients at risk for cardiovas
cular morbidity.