(Philadelphia, PA) University of Pennsylvania School of Medicine researchers have found additional evidence that may help explain how selective inhibitors of COX-2 might predispose individuals to heart disease and stroke. In Circulation Research, they report that a COX-2-derived fatty substancea prostaglandin called prostacyclincontrols the blood-vessel response to stresses such as high-blood pressure, thereby further linking COX-2 inhibitors to an increased risk of heart attack or stroke. This knowledge, along with a growing literature on physiological responses to COX-2 inhibitors, should help in the development of a rational approach to clinical risk management for this class of drugs.
Two randomized trials of COX-2 inhibitorsthe gold standard of clinical evidenceconducted in 2004 at other institutions suggested that risk of cardiovascular disease might increase gradually during continued treatment with drugs such as Celebrex and Vioxx, even in individuals initially at low risk of the disease.
"The risk of heart attack and stroke became progressively evident during treatment with either Celebrex or Vioxx during the APPROVe and APC trials last year," says Garret FitzGerald, MD, lead author of the study published online last week. FitzGerald is the Director of the Institute for Translational Medicine and Therapeutics at Penn.
These studies were designed to determine whether COX-2 inhibitors limited the development of benign growths in the large bowel of patients whoto the best of study authors' knowledgewere at low risk of heart disease. "While the results of these trials are not conclusive, they are compatible with a gradual transformation of increased cardiovascular risk during continued dosing with either Celebrex or Vioxx," says FitzGerald. "We need to determine how this might occur, and whether we can manage this risk by developing tests that reflect the process."
Earlier animal studies by Penn researchers and others showed tPage: 1 2 3 Related medicine news :1
Contact: Karen Kreeger
University of Pennsylvania School of Medicine
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