Penn epidemiological study shows difference in cardiovascular effects between Vioxx and Celebrex

December 06, 2004

(Philadelphia, PA) -- 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.

As part of their case-control study, the research team solicited relevant data from 36 hospitals in a five-county area about patients who had been discharged following hospitalization for a nonfatal myocardial infarction (MI), or heart attack, between May 1998 and December 2002. The researchers then queried those patients (within four months of their hospitalization for MI) about their use of COX-2 inhibitors or NSAIDs immediately prior to their heart attack. As a control, the investigators performed structured telephone interviews with 6,800 individuals who were randomly selected from the same counties as the previously hospitalized patients. The study was carefully designed to address factors that would influence the results -- including patients' body mass index (BMI), physical activity, and recall bias.

Despite the careful planning of the study, definitive conclusions about the risk of heart attacks from rofecoxib or celebrex relative to people who did not use the drugs cannot be made from this nonrandomized study. However, the comparison between the drugs is much more likely to be accurate. "Further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors," Kimmel adds.
-end-
The study was supported by grants from the National Institutes of Health, Searle Pharmaceuticals (now Pfizer, Inc.), and Merck & Co., Inc. Kimmel has consulted for Pfizer on matters unrelated to COX-2 inhibitors.

PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation's first integrated academic health system).

Penn's School of Medicine is ranked #3 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three owned hospitals [Hospital of the University of Pennsylvania, which is consistently ranked one of the nation's few "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Presbyterian Medical Center]; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

University of Pennsylvania School of Medicine

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