Address of Corresponding Author

J Vasc Res 2005;42:312-324 (DOI: 10.1159/000086459)

  Key Words

• Atherothrombosis
• Cyclooxygenase
• Platelets
• NSAID
• Cyclooxygenase-2

  Abstract

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 (PGI₂), 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.

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Dr. Florian Krötz
Cardiology, Medical Polyclinic, Ludwig Maximilians University
Ziemssenstrasse 1
DE-80336 Munich (Germany)
Tel. +49 89 218075 384, Fax +49 89 218075 378, E-Mail florian.kroetz@med.uni-muenchen.de

  Article Information

Received: January 31, 2005
Accepted after revision: April 8, 2005
Published online: June 20, 2005
Number of Print Pages : 13
Number of Figures : 3, Number of Tables : 1, Number of References : 96