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December 19, 2004

Cardiovascular risk and COX-2 inhibition in rheumatological practice.

Topics: Clinical Pharmacology

Cox-2 inhibitors are in the news having now heard concerns over both Vioxx and Celebrex. So it seems appropriate to look at a recent article on Cox-2's - no light bulbs in this one but enough information to justify a conservative approach to utilizing this class of drug until more information is available.

Abstract review, J Hum Hypertens. 2005 Jan;19(1):1-5, Justice E, Carruthers DM.
Department of Rheumatology, Sandwell and West Birmingham Hospitals Trust, City Hospital, Birmingham, UK.

The use of specific COX-2 inhibitors in place of standard nonsteroidals for the treatment of arthritis appears to reduce the risk of serious gastrointestinal toxicity in this group of patients. However, the role played by these inhibitors in the generation or exacerbation of ischaemic cardiovascular disease is less clear. Clinical studies demonstrate that hypertension can be induced or aggravated by COX-2 inhibitors to a degree similar to that which occurs with standard nonsteroidals. Endothelial dysfunction, an indicator of cardiac ischaemia, may also be exacerbated by specific COX-2 inhibition and there is much debate as to whether these changes lead to an absolute increase in ischaemic cardiac events. These effects on cardiovascular risk factors appear all the more important in patients with rheumatoid arthritis where there is an increase in the incidence of ischaemic heart disease. Here we review the available data on COX-2 inhibition and cardiovascular disease and conclude that all patients who started these agents should have a careful assessment and modification of any cardiovascular risk factors.Journal of Human Hypertension (2005) 19, 1-5. doi:10.1038/sj.jhh.1001777 Published online 23 September 2004. 
PMID: 15385947 [PubMed - in process]

Black Triangle cross posted on this topic today, as did Medpundit. Medpundit's comments indicated a hesitation to prescribe Cox-2 inhibitors in our litigous-conscience society (my words not hers). Based on what little we know to support a decision to treat that would be based upon positive risk/benefit evidence, such a decision on her part could most likely be considered sound medical practice due to doubt on a favorable risk/benefit ratio alone, at least under the conditions described. The matter of malpractice considerations tips the balance solidly against the physician. Ergo, I wouldn't be buying any stocks on the basis of futures for Cox-2 inhibitors until more solid research evidence is available that supports safety in moderate risk patients, let alone in the case of high risk patients.

Also see "Is there a future for Cox-2 inhibitors," Harefuah. 2004 Nov;143(11):820-4, 837.

Update: Derek Lowe at In the Pipeline has a good discussion on the Celebrex issue entitled "The FDA Weighs In."
Update 2: Black Triangle has a summary update with links to various resources for information on Cox-2 inhibitors.

Posted by Hyscience at December 19, 2004 1:48 AM



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