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Title: Valdecoxib Linked to Cardiovascular Complications: Presented at AHA

"Valdecoxib Linked to Cardiovascular Complications: Presented at AHA"

By Charlene Laino NEW ORLEANS, LA -- November 11, 2004 -- The cyclooxygenase-2 (COX-2) inhibitor valdecoxib (Bextra) more than doubles the risk of myocardial infarction (MI) and strokes, according to the author of a pooled analysis. But Pfizer Inc., manufacturer of valdecoxib, said the study "draws unsubstantiated conclusions" about the cardiovascular safety of the COX-2 inhibitor and is based on information that has not been published in a medical journal or subject to independent scientific review. Garret Fitzgerald, MD, PharmD, Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania discussed the findings at press conference here on November 10[^th at the American Heart Association Scientific Sessions 2004. He said that the pooled analysis was conducted after two smaller studies of valdecoxib in coronary artery bypass patients suggested a class effect of COX-2 inhibitors on risk of cardiovascular complications.

Merck recently withdrew rofecoxib (Vioxx) from the market after a controlled study showed that the drug doubled the risk of MI and stroke.

Dr. Fitzgerald's analysis, which has not been peer reviewed but was described in an invited lecture at the AHA meeting on November 9^th, pooled data from the two studies of patients who underwent coronary artery bypass graft (CABG) procedures and another meta-analysis of randomized controlled trials of valdecoxib in arthritis patients.

In all, there were 2098 patients in the bypass studies and 5673 patients in the arthritis studies. Of those, 5930 patients were randomized to valdecoxib and the 1841, placebo.

Among bypass patients taking valdecoxib, 31 had MIs or strokes, compared to five MIs and strokes in the placebo arm, he said. Among the arthritis patients, there were 14 MIs and strokes in the valdecoxib arm and two in the placebo arm, Dr. Fitzgerald said.

"When the data were pooled, the risk for myocardial infarctions and strokes was more than twice as high in the valdecoxib arm, compared with the placebo arm," Dr. Fitzgerald said. Specifically, the relative risk was 2.19, with a confidence interval of 1.19-4.03 and a P value of.01.

"While a statistical test for heterogeneity was not significant, I would not put too much stock in that," he said. Rather, the fact that cardiovascular complications were first observed in bypass patients speaks to a class-specific effect with a common mechanism at play, he added.

"The likelihood that you will detect a cardiovascular signal is directly related to the degree to which the thrombotic system is activated," he explained. "So if the risk of thrombosis is heightened, you would expect to see an effect more quickly. CABG is the canary in the coal mine."

Pfizer noted that a peer-reviewed analysis published earlier this year in the American Journal of Therapeutics that included nearly 8,000 patients treated with valdecoxib for 6 to 52 weeks showed that short- and intermediate-term treatment with valdecoxib was not associated with an increased incidence of thrombotic events relative to nonselective NSAIDs (nonsteroidal anti-inflammatory drugs) or placebo in osteoarthritis and rheumatoid arthritis patients.*

* Reference
White WB, et al. "Effects of the Cyclooxygenase-2 Specific Inhibitor Valdecoxib Versus Nonsteroidal Antiinflammatory Agents and Placebo on Cardiovascular Thrombotic Events in Patients with Arthritis." Am J Ther. 2004; 11(4): 244-250.

[Presentation title: "2004 Russell Ross Memorial Lectureship in Vascular Biology: Bioactive Lipids and Atherothrombosis."]

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