More Evidence of How Cox-2’s Can Raise Heart Risks

Six years ago Dr. Garret FitzGerald, 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 initially based on his studies of how Celebrex® and Vioxx® worked in human volunteers.

The first unequivocal evidence of this risk emerged with the Merck-sponsored APPROVe study of Vioxx®, leading to the withdrawal of the drug in September of last year. Evidence implicating a second Cox-2 drug, Bextra®, was presented by FitzGerald in a lecture at the American Heart Association in November of 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.

In two recent articles, published in Circulation, researchers from the University of Pennsylvania School of Medicine including FitzGerald, provide further evidence for the role of Cox-2 inhibitors in heart-disease risk.

In the first article 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. The statistical approach of meta-analysis used by FitzGerald combined the findings of two trials to obtain a stronger estimate of the risk of heart attack plus stroke than is possible from looking at either trial alone.

In the second study researchers studied mice genetically prone to hardening of the arteries or atherosclerosis and found that a compound called thromboxane or TxA2, produced by Cox-1, accelerates atherosclerosis. "This is of particular interest, as low-dose aspirin prevents heart attack and stroke by blocking Cox-1 and the formation of TxA2 in blood cells called platelets," FitzGerald said in a statement.

When a Cox-2 inhibitor was added, something happened that may help explain why Cox-2 inhibitors raise the risk of heart attack, said FitzGerald’s colleague, Karine Egan. "Addition of the Cox-2 inhibitor caused changes that, if they occurred in humans, would result in a loss of stability of the plaque, making it more likely to rupture and activate clotting, causing heart attack or stroke," she said.

"These results would have disturbing implications for patients at high cardiovascular risk treated with aspirin and a Cox-2 inhibitor," FitzGerald said.

The studies and papers were funded in part by grants from the National Institutes of Health, Servier Laboratories, and Merck Research Laboratories. Servier and Merck had no influence on the design or interpretation of the studies, and the authors have no competing financial interests.

If you or a loved one were injured through the use of a pharmaceutical product or dietary supplement please use the form below to contact our law firm.

Your Name (required)

Your Email(required)

Phone Number (required)


Your Message


Enter the text above to validate your message