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 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.