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.