In the first epidemiological study designed and executed specifically to determine the heart-attack risk associated with COX-2 inhibitors rofecoxib (Vioxx) and celecoxib (Celebrex), researchers at the University of Pennsylvania School of Medicine found a greater risk of heart attack associated with Vioxx than Celebrex, although neither of the two drugs showed a statistically significant elevated risk of heart attack relative to people who did not use the drugs. In addition, the researchers found discrete clinical differences between the two COX-2 inhibitors -- which suggest that the effect of the drugs on the cardiovascular system should be viewed separately rather than as a single class of drugs. This study appears online December 7, 2004 and will be published in the February 1, 2005 print issue of the Annals of Internal Medicine.
The study, which also compared the heart-attack risk between COX-2 inhibitors and older nonsteroidal anti-inflammatory drugs (NSAIDs), found a lower risk with NSAIDs rather than COX-2 inhibitors. The NSAIDs studied included aspirin, ibuprofen (Advil and Motrin), and naxproxen (Aleve). "Our results suggest that there is a marked difference between rofecoxib and celecoxib relative to heart-attack risk," said Stephen E. Kimmel, MD, Associate Professor of Medicine at Penn and lead author of the study. Use of rofecoxib was associated with 2.72-higher odds of heart attack than was the use of celecoxib. That difference, Kimmel suggests, may be due to a number of factors, including differences in selectivity for the COX-2 isoenzyme, blood pressure, endothelial function, and oxidative stress. Rofecoxib was also associated with a higher odds of heart attack compared with older NSAIDs.
The study also demonstrated a lower risk of heart attacks among people using Celebrex relative to people who did not use other NSAIDs, but Kimmel notes that "this could be just a fluke." Regardless, there was no evidence for an increased risk from Celebrex, again suggesting differences within the class of COX-2 inhibitors.
Karen Kreeger | EurekAlert!
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