Researchers at Queen's University and the University of Pennsylvania have identified one reason why drugs like Celebrex and Vioxx - once popular for the treatment of pain and inflammation - cause heart problems.
Their findings offer the prospect of a new generation of anti-inflammatory drugs that will bypass this issue, says co-author Colin Funk, a professor of Biochemistry and Physiology at Queen's, and Canada Research Chair in Molecular, Cellular and Physiological Medicine. Although these results are in mice, not people, they raise an exciting possibility which can be tested in humans, he adds.
The study is published in the on-line edition of the Journal of Clinical Investigation.
Since the association of selective inhibitors of COX-2 such as Vioxx, Bextra and Celebrex with an increased incidence of heart attack and stroke, there has been intense interest in understanding the mechanism involved. Clarification of this issue offers the prospect of conserving the clinical benefit of these drugs for patients with arthritis, while managing the risk, the researchers say.
Co-author with Dr. Funk on the study is Dr. Garret FitzGerald, director of Penn's Institute for Translational Medicine and Therapeutics. Funding comes from the U.S. National Institutes of Health and a grant from Merck.
The investigators first compared genetically manipulated mice that mimic the impact of either COX-2 inhibitors or low-dose aspirin with healthy mice treated with or without COX-2 inhibitors, such as Celebrex. "The trials showed that COX-2 inhibitors confer a small, but absolute cardiovascular risk using the same mechanism by which they relieve pain and inflammation," Dr. Funk reports.