Editorial urges 'black-box' warning for Bextra and Celebrex

Physicians should avoid prescribing Bextra altogether, or use it only as a drug of last resort, says a researcher from
Wake Forest University Baptist Medical Center and colleagues in an editorial published on-line Jan. 17 in Circulation, a
publication of the American Heart Association.


Curt D. Furberg, M.D., Ph.D., professor of public health sciences, and colleagues describe an analysis of two studies
revealed that patients treated with Bextra after heart bypass surgery tripled their risk of heart attack and stroke compared
to patients who received a placebo, or "dummy" drug. The data is a followup to information reported at the American Heart
Association meeting in November.


"These data raise questions about the safety of the drug in other patients who have heart conditions, but who aren't having
surgery," said Furberg. "In the absence of evidence of safety, it is prudent to avoid the use of Bextra altogether or use it
only as a drug of last resort," says the editorial. Furberg's co-authors are Bruce M. Psaty, M.D., Ph.D., from the University
of Washington in Seattle, and Garret A. FitzGerald, M.D., from the University of Pennsylvania.


The researchers say the Bextra results, combined with studies showing cardiovascular hazards with Celebrex and Vioxx,
"provide compelling evidence that these adverse coronary and cerebrovascular events represent a class effect…" The drugs are
all part of a class called COX-2 inhibitors.


"A black-box warning that alerts practitioners to the potential cardiovascular hazards, especially in patients at moderate to
high risk, seems timely for all COX-2 inhibitors," said Psaty.


Furberg supports the advice of the Food and Drug Administration, which issued a Public Health Advisory on COX-2 inhibitors
and other non-steroidal anti-inflammatory drug products urging physicians to weigh the benefits against the risk for
individual patients.


In the editorial, the authors support research to learn whether the drugs can be safely given for extended periods to
patients at low risk of cardiovascular disease.


"It is currently unclear to what degree the risk extends to patients treated with lower doses for arthritis because studies
of sufficient size and duration have not been reported," Furberg said.


FitzGerald, who has been studying COX-2 inhibitors for more than six years, says that plans by Pfizer to study potential
cardiovascular benefits of Celebrex are ill-advised.


In a separate article in Circulation, FitzGerald and colleagues report on evidence from mice showing that the combination of
aspirin and a COX-2 inhibitor could make plaque in the arteries more likely to rupture and cause clotting, resulting in heart
attack or stroke.


"These results have disturbing implications for patients at high cardiovascular risk treated with aspirin and a COX
inhibitor," writes FitzGerald.


Media Contacts: Karen Richardson, krchrdsnwfubmc; Shannon Koontz, shkoontzwfubmc; at 336-716-4587


About Wake Forest University Baptist Medical Center:


Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University
Health Sciences, which operates the university's School of Medicine. The system comprises 1,282 acute care, psychiatric,
rehabilitation and long-term care beds.


Karen Richardson

krchrdsnwfubmc

Wake Forest University Baptist Medical Center


View drug information on Bextra; Vioxx.