| October
3, 2004
Vioxx® pulled
from market: But is this reason to
celebrate?
By Dr. James D.
Chlovechok
The cable news channel I was watching
today proclaimed the startling news that
Merck had withdrawn its
multi-billion-dollar arthritis drug,
Vioxx®, from shelves worldwide because
the medication had been linked to severe
and even fatal heart complications. The
report advised anyone taking Vioxx® to
contact their physicians about
prescribing alternative medications. The
station then broke immediately to a
commercial for Celebrex®.
As a physician who has been cautioning
patients about the ills of both
medications, I did not feel the urge to
dance like the stars of so many
commercials for arthritis remedies. Both
Celebrex® and Vioxx® are known as COX-2
inhibitors, a sub-class of non-steroidal
anti-inflammatory drugs, or NSAIDS. Older
NSAIDS include ibuprofen, naproxen,
indomethacin, and many others, including
the prototype aspirin.
Facts:
-- In 1998,
fatalities due to NSAIDS among arthritis
sufferers rivaled deaths from AIDS.
-CHF from NSAIDS may have exceeded GI
toxicity, which already accounted for
107,000 admissions per year.
-- NSAIDS were
called a silent epidemic by a prestigious
medical journal, and then, incomplete and
misleading data published in another
leading journal turned newer, but still
unimproved, substitutes into a
multi-billion-dollar industry.
-- NSAIDS inhibit
enzymes in the body called
cyclooxygenase, of which there are two
sub-types: COX-1 and Cox-2. The older
NSAIDS block both, while the newer ones
target only COX-2. Why is this important?
-- According to
the New England Journal of Medicine, in
1998 NSAIDS accounted for 16,500 deaths
in the U.S. among arthritis sufferers
alone, and 107,000 people were
hospitalized due to NSAID-related
bleeding from the stomach or bowels. The
journal editors called this a “silent
epidemic.”
-- The deaths
among arthritis sufferers due to NSAIDS
approached all deaths in this country
from AIDS that year—and far exceeded
deaths from breast cancer, leukemia,
lymphoma, or several other feared killers
combined. Worse, the numbers did not
include over-the-counter preparations or
uses such as headache, backache, dental
pain, menstrual or postoperative pain, or
many others.
-- While retired
athletes pitched Advil® on television,
and physicians wrote thousands upon
thousands of new NSAID prescriptions,
where were the lapel ribbons,
fundraisers, or public awareness
campaigns concerning this killer?
-- Physicians
have been aware of at least one dangerous
NSAID complication: GI bleeding. But this
was felt to be due to inhibition of the
COX-1 enzyme. Hence, the search for
selective COX-2 blockers. And in 1999—the
year after the New England Journal
editorial—Vioxx® and Celebrex® hit
the streets running. Hailed as safer,
both were said to lower the incidence of
stomach ulcer and bleeding. Physician
offices and professional journals were
bombarded with this news. Billions of
dollars of prescriptions were written.
But the whole story had not been told.
-- Bleeding is
not the only side effect associated with
NSAIDS. In March 2000, the Archives of
Internal Medicine speculated: “The
burden of illness from NSAID-related CHF
(congestive heart failure) may exceed
that resulting from gastrointestinal
damage.” Other studies indicate half
of all hospital admissions for CHF may be
due to NSAIDS. And yet this and other
potential side effects were ignored by
the researchers and marketers hailing
Vioxx® and Celebrex®
Both drugs were denied labeling that
would indicate a safety advantage.
The possibility of other side effects did
not escape the FDA. Neither did data from
the manufacturers’ own safety
studies. Why? For Vioxx®, fewer patients
suffered GI bleeding compared to an older
NSAID, but total serious adverse events
were actually higher in subjects taking
Vioxx®. And the famed Celebrex® CLASS
study, published in the Journal of the
American Medical Association (JAMA),
turned out to actually be combined data
from three separate studies. And the
lower rate of ulcer bleeding was
preliminary. That’s right. The
studies were not even complete.
Celebrex® users indeed had fewer ulcers
and GI bleeds in the first half of the
study, but they had more in the second
half—and the numbers balanced out.
More shocking, the overall risk of death
or adverse effect was higher in those
taking Celebrex® than in those taking
the non-specific NSAID.
So, the miraculous safety advantage of
either of these new drugs is a myth. Even
before Vioxx® was pulled, the FDA had
sent warning letters to the both Merck
and Pharmacia, maker of Celebrex®,
regarding deceptive marketing practices.
But what about benefit? According to
efficacy studies, eight patients would
have to take Vioxx® for eight weeks to
experience a 20% decrease in joint
swelling. And studies of Celebrex®
showed it to be roughly equivalent to
naproxen in reducing arthritis joint
pain. No NSAID has ever been shown to
favorably alter the course of any
arthritic condition; in fact, while these
drugs may temporarily decrease pain, the
studies I have seen demonstrated more
rapid destruction of joint tissues with
NSAIDS.
In this country, we have come to expect a
lot from medical science and our
physicians. Unfortunately, most of the
science is being financed by those with
money riding on experimental results. And
these industrial giants answer not to
individual patients, but to stockholders.
Physicians answer to
patients, but receive much of their
research information via slanted
industrial marketing. And patients are
coached through media advertising to
“ask your physician about” this
or that drug, or to report symptoms that
coincide with a list of indications for
prescribing the preferred medication. And
this list will have been conveniently
dropped off at my office along with some
free samples, a few ink pens, and
chocolates for my office staff.
I think it is good that Vioxx® has been
withdrawn. But I am not yet ready to
celebrate a healthcare system that puts
marketing so far in front of science, or
profits ahead of patients’
interests.
_______________________________________________
James D. Chlovechok, M.D., is a former
Assistant Medical Director for a major
bio-pharmaceutical company and the
current Medical Director of the Ohio
Sports Medicine Institute. He is working
on a book dealing with NSAID risks. Visit
him at http://www.doctorjim.org/
Chlovechok is also the author of Game
Face, an intense, fast-paced novel that
blends mystery and sports, medicine and
murder—a book that takes you behind
the scenes where athletes will do
anything to win—even if it kills
them.
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