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Withdrawal of Vioxx
and the COX-2 Debate
As
many of you have heard from newspapers, television,
friends or other health care providers, the arthritis
medication Vioxx (rofecoxib) has been voluntarily
withdrawn from the market by its manufacturer Merck
& Co. This was done after a recent 3 year study showed
an increase risk of heart attack and stroke in patients
taking Vioxx compared with those taking a placebo
(sugar pill). This confirmed the results of other
recent studies that also showed a possible increased
risk of cardiovascular problems (heart attack and
stroke) with Vioxx. If you are still on Vioxx you
should stop the medication and call our office.
Many
of our patients have taken Vioxx since its approval
in 1999, and several of us have authored research
studies on Vioxx. We understand that our patients
may be concerned and confused about this new information
and we would like to take this opportunity to share
our experience, thoughts and scientific expertise.
Non-steroidal
anti-inflammatory medications (NSAIDs) work by inhibiting
the enzyme cyclo-oxygenase. In 1990 it was discovered
that there are 2 forms of cyclo-oxygenase, dubbed
cox-1 and cox-2. Cox-1 is found in the lining of the
stomach and plays a role in protection of the stomach
against acid. Cox-1 also helps blood to clot. Cox-2
is produced in inflammation. The older NSAIDs (aspirin,
ibuprofen, naproxen, diclofenac, etc) all inhibit
both Cox-1 and Cox-2. Thus these agents are effective
anti-inflamamtory agents, but they also can thin the
blood and have the side effect of increased bleeding,
particularly from the stomach. These non-specific
NSAID's can cause gastrointestinal ulcers at a rate
as high as 1% per year. Vioxx (rofecoxib), Celebrex
(celecoxib) and Bextra (valdecoxib) are all members
of a subclass of NSAID medications called selective
Cox-2 inhibitors. Because they selectively inhibit
Cox-2 they do not block the helpful "housekeeping"
functions of cyclo-oxygenase, and are therefore effective
anti-inflammatory medications but with a lower risk
of gastrointestinal (GI) bleeding.
There
were 3 recent, prominent studies that led to the withdrawal
of Vioxx. Two studies were observational studies.
Both looked at large computer databases of patients
and identified patients who had heart attacks and
strokes. The investigators then looked at whether
those patients had been taking Vioxx, Celebrex, or
other NSAIDs. Both those studies showed that taking
Vioxx was associated with an increase risk of heart
attacks and strokes. Celebrex or other NSAIDs did
not show an increased risk. However, observational
studies are often difficult to interpret because additional
information about the patients (other medical problems,
other medications) is lacking. However, the most recent
study was a clinical trial of 2600 patients who were
receiving either Vioxx or placebo to test whether
Vioxx could prevent colon polyps. In this study, after
18 months, the patients taking Vioxx had more heart
attacks and strokes than those taking the placebo.
This evidence from a controlled clinical trial ultimately
led to the decision by Merck to withdraw the drug.
The
cause of the increased cardiovascular risk remains
unclear. Although Celebrex and Bextra are both Cox-2
inhibitors, the same class as Vioxx, none of the prior
studies with these drugs have shown an increased risk
of heart attacks or stroke. The incidence of heart
attack and stroke seen in the studies was low. The
risk of cardiovascular problems is decreased by the
use of low dose aspirin and thus patients who are
at risk for heart attack or stroke should take low
dose aspirin with Celebrex or Bextra if advised by
their doctor. There is also no evidence to suggest
that the increased cardiovascular risk persists after
Vioxx is stopped.
Problems
with one member of a drug class may not affect other
members of the class. Nonetheless, further studies
with Celebrex and Bextra are being evaluated and planned
by the FDA and other investigators. We will be watching
for this new information carefully. We are hopeful
that these drugs and other new drugs of its class
will be proven safe as they have provided significant
benefit for our patients, particularly those who have
had GI bleeding or GI intolerance to other older non-steroidal
medications.
If
you have further questions, or need specific advice
about your particular situation please contact your
physician at Arthritis and Rheumatism Associates.
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