DOCTOR'S VIEW ARCHIVE
Cox-2 Inhibitors, What's Next?
Cox-2 Inhibitors After FDA/Arthritis Advisory Committee
Meeting February 16-18, 2004 ...Vioxx, Celebrex, Bextra
Medical Author: William C. Shiel, Jr, FACP, FACR
On February 16-18, 2005, a joint
meeting of the Arthritis Advisory Committee and the Drug Safety and Risk
Management Advisory Committee of the FDA Drug Safety Committee ("committee") was
convened to review the safety of COX-2
including rofecoxib (Vioxx),
celecoxib (Celebrex), and valdecoxib (Bextra) NOTE: April 7, 2005, Pfizer has agreed to suspend sales and marketing of Bextra in the U.S., pending further discussions with the with the FDA. For more information, please read the
FDA press release.
. The committeesreviewed the details of
research studies and specifically evaluated the risks of these drugs in regard
to heart attack and stroke. They also reviewed other antiinflammatory drugs
Eight of the 32 voting panelists
were arthritis specialists (rheumatologists) and the results of the meeting were
summarized by the American College of Rheumatology (ACR) as follows:
- A clinical trial using naproxen in patients with Alzheimer's
disease noted an increased risk of heart attack and stroke and was halted.
According to the advisory panel, the study was stopped because of media
attention and not because of an unacceptable safety signal. The data in that
study seems to indicate that the numbers were inadequate to come to the conclusion that there
was an increased risk of heart attack or stroke in that study. In fact, a number
of studies indicated a decrease in the risk of heart attack and stroke
when taking naproxen.
- The committee unanimously voted that all of the cox-2 inhibitors
significantly increase the risk of heart attack and stroke. The cox-2
inhibitors that are currently on the market in the U.S. are celecoxib (Celebrex) and
valdecoxib (Bextra). The committee also agreed unanimously that Celebrex should be kept
on the market for its current uses. Regarding Bextra, the committee voted 17
in favor of keeping this drug on the market, 13 not in favor, and 2
- The committee agreed unanimously that a "black box"
warning should be added to the labeling of
each cox-2 inhibitor that would clearly indicate the increased risk of heart attack and stroke.
Furthermore, they recommended that this warningadvise that these drugs should be
avoided in patients with a high riskfor heart attack or stroke due to
the presence of other risk factors.
- The balancing of risks versus benefits of the cox-2 inhibitors
favors their continued use.
- While all nonsteroidal antiinflammatory drugs have the potential for causing
heart attacks and strokes, the relative risks are not the same. For example,
naproxen and Celebrex seem to have less risk than Vioxx or Bextra.
- The risks of heart attack and stroke with cox-2 inhibitors may be
greater when the drugs are used in higher doses, for longer periods of time,
and in high risk individuals.
- The use of cox-2 inhibitors should be avoided in
patients with a high risk for heart attack and stroke due to the presence of other risk
factors for heart attack and stroke.
What will happen next?
The FDA will now review the findings and recommendations of the Advisory
Panel. It is expected that the recommendations will be adopted and
implemented. If so, there likely will be a tremendous wave of education
directed at both physicians and healthcare personnel as well as patients.
A wide variety of clinical research trials will be forthcoming
that will further clarify the safety issues of all
antiinflammatory medications. Moreover, new antiinflammatory medications will be required
to undergo clinical trials that focus on the risks of heart attack and
stroke before being marketed in the U.S.
There is a great deal of uncertainty as to whether or not
Vioxx will reenter the U.S. market. If it does, it will certainly carry
"black box" warnings regarding its potential to cause heart attack and stroke.
Last Editorial Review: 4/7/2005
American College of Rheumatology, (www.rheumatology.org/hotline)