In two articles, published in Circulation, researchers from the University of Pennsylvania School of Medicine provide further evidence for the role of cyclooxygenases (COX) in heart-disease risk. In one, a statistical meta-analysis of two placebo-controlled trials, the COX-2 inhibitor Bextra elevated the combined incidence of heart attack and stroke three-fold in coronary artery bypass graft (CABG) surgery patients. In the second, the investigators found that a fat produced by COX-1 speeds hardening of the arteries in a mouse model of atherosclerosis, which may have implications for low-dose aspirin therapy in heart patients.
Six years ago Garret FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at Penn, raised the possibility that selective COX-2 inhibitors might predispose patients otherwise at risk for an increased incidence of heart attack and stroke. This proposal was based initially on his studies of how celecoxib (Celebrex) and rofeocoxib (Vioxx) worked in human volunteers.
The first unequivocal evidence of this risk emerged with the Merck-sponsored APPROVe study of Vioxx, leading to withdrawal of the drug in September 2004. Evidence implicating a second member of the class, valdecoxib (Bextra) was presented by FitzGerald in a lecture at the American Heart Association (AHA) in November 2004. This work – a collaboration led by Curt Furberg of Wake Forrest University, along with Bruce Psaty of the University of Washington and FitzGerald – appears online January 17 in Circulation and in the January 25th print edition of the journal.
Karen Kreeger | EurekAlert!
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