June 2005 BMJ Article Calls Into Doubt Cardiovascular Safety of All NSAIDs

There is new evidence that all selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of having a heart attack, or myocardial infarction (MI).  This evidence comes from work done by Dr. Julia Hippisley-Cox and Dr. Carol Coupland, who are associated with the University of Nottingham, in the UK.  The results of their recent observational study — which the authors describe as a population-based nested case-control study using the QRESEARCH database of information from UK general practices — is reported their in the June 11, 2005 issue of the British Medical Journal (BMJ).

Most noteworthy, perhaps, is the study’s finding that diclofenac and ibuprofen seem to pose about as much risk as Vioox (rofecoxib), the COX-2 inhibitor which was withdrawn from the market in September 2004.  The adjusted odds ratio (OR) for Vioxx use within the 3 months before a first heart attack was 1.32; for ibuprofen that adjusted OR was 1.24, and for diclofenac the OR was 1.55 (p < 0.01).  For their study, the authors looked at 9218 cases of a first MI in people between the ages of 25 and 100 during study period from 2000 to 2004, and 86,349 controls matched by age, calendar time, gender and practice. 

Dr. Hippisley-Cox and Dr. Coupland note in their June 2005 BMJ article:

Given the high prevalence of the use of these drugs in elderly people and the increased risk of myocardial infarction with age, even the relatively large number of patients needed to harm could have considerable implications for public health.

Accordingly, Dr. Hippisley-Cox and Dr. Coupland reach this conclusion: "We think that enough concerns exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs."

An associated editorial in the same June 11 issue of the BMJ, however, urges that reaction to this apparent new evidence presented by Dr. Hippisley-Cox and Dr. Coupland be held in check.  Dr. Peter Juni, from the University of Berne in Switzerland, and some of his colleagues advise in their BMJ editorial that the data from this recent article must be "interpreted with caution," given that the underlying study is observational in method, and other drug-safety trials involving NSAIDs have yielded vastly different end results.

(Posted by: Tom Lamb)