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(Circulation. 2005;111:249.)
© 2005 American Heart Association, Inc.

Editorial

Parecoxib, Valdecoxib, and Cardiovascular Risk

From the Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.D.F.); the Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Wash (B.M.P.); and the Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia (G.A.F.).

Correspondence to Curt D. Furberg, MD, PhD, Professor, Department of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1063. E-mail cfurberg@wfubmc.edu

Key Words: Editorials • drugs, antiinflammatory • inflammation • safety, consumer product

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Selective inhibitors of cyclooxygenase (COX)-2¹ depress prostacyclin (PGI₂) but not COX-1–derived thromboxane A₂. The effects of thromboxane A₂ would be exaggerated during treatment with COX-2 inhibitors, potentially predisposing patients to heart attack and stroke.²

A randomized controlled trial in patients undergoing coronary artery bypass graft (CABG) surgery and receiving either placebo or 40 mg parecoxib (Dynastat; Pfizer), the intravenously administered prodrug of valdecoxib (Bextra; Pfizer), followed by oral valdecoxib 40 mg BID for 14 days, revealed a cluster of cardiovascular events.³ In a second study, one group received parecoxib/valdecoxib, another intravenous placebo followed by valdecoxib (20 mg BID for 10 days), and the third placebo alone. Despite the reduction in dose and duration of therapy, a cluster of events was again apparent. Data from the second trial are in the new label for valdecoxib.⁴

The Table represents the incidence of coronary and cerebrovascular events in the two trials individually and combined in a meta-analysis.⁵ The two active treatment arms of the unpublished trial were combined and compared with placebo. Although the treatment–placebo difference did not reach conventional levels of statistical significance for the individual trials, valdecoxib in the combined analysis was associated with a 3-fold higher risk of cardiovascular events than placebo. There was no statistical evidence of heterogeneity.

Parecoxib is only known to afford pain relief by its rapid transformation to valdecoxib in vivo, and valdecoxib has selectivity for inhibition of COX-2 in vitro that approximates that of rofecoxib. A PGI₂. . . [Full Text of this Article]

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