Hold the party: The alternatives to traditional
NSAIDs need more study
By Christopher Chaput, M.D.
Mrs. Harriet said she was in my office because the weather had
changed. "These old knees are aching me something terrible," she
lamented as she showed me her bowed legs, typical of advanced
osteoarthritis. "I've got to have something to help me get around
when my arthritis flares up like this." Mrs. Harriet was living
alone and wanted to continue her independent lifestyle. "Listen
to these things," she said, bending her knees. "Have you ever
heard such creaking?"
While Mrs. Harriet told me about her pain, I flipped through
her chart and saw she was more frail than she looked. She had
congestive heart failure, coronary artery disease, and diabetes.
She had been in and out of the hospital a couple of times for
chronic bronchitis that bloomed into pneumonia. She still smoked
"a cigarette or two" a day and somehow managed to keep track of
her ten or so prescription medications well enough to hold her
medical conditions under fair control.
I saw some notes from other orthopedists. Mrs. Harriet had tried
most of the standard therapies for arthritis -- including steroid
injections into the knees, nonsteroidal anti-inflammatory drugs,
canes, and bracing -- as well as the alternative treatment glucosamine.
"Did anything help?" I asked.
"That big pill helped some. But it almost killed me," she said,
smiling. She meant her pain reliever; about a year ago Mrs. Harriet
was admitted for a three-week stay in the intensive-care unit
after vomiting up a significant amount of blood. The most likely
cause of the bleeding was the prolonged use of nonsteroidal anti-inflammatory
drugs (NSAIDs) such as ibuprofen, naproxen, or ketoprofen. She
had been taking these medications for more than a year.
I began to offer Mrs. Harriet alternatives: "There is always
joint replacement, but I'm not sure your heart and lungs would
be able to take it. It's a big surgery." She wasn't interested
in surgery, but she was interested in a new drug called celecoxib,
known by the brand name Celebrex. She had heard, as had I, that
this new breed of NSAID was supposed to be much easier on the
NSAIDs: Over 30 million served
Nonsteroidal anti-inflammatories are relatively safe when taken
for limited periods of time and under the supervision of a physician.
The most common serious problems linked to NSAIDs include ulcers,
gastrointestinal bleeding, and intestinal perforation. These drugs
can have more serious side-effects, however, such as kidney failure,
bleeding and clotting problems during surgery, and quite a list
of less common complications. Every treatment comes at a price,
and with NSAIDs, that price can be rather steep.
Thirty million patients a day use NSAIDs, making them the most
commonly prescribed type of medication in the world. Perhaps as
a result, they (by some estimates) cause the highest number of
reported serious complications of all medications. Every year,
nearly four billion dollars a year are spent treating these complications
and about 7,600 people actually die from them.
Patients like Mrs. Harriet are at significant risk; the elderly
and those with chronic health problems who must take these drugs
for long periods of time to control pain often end up with NSAID-related
complications. According to one study, up to 40 percent of elderly
patients receive prescriptions for NSAIDs.
Celebrex is among a new class of NSAIDs called COX-2 inhibitors,
which were developed in response to the potentially serious side
effects of common anti-inflammatories. COX-2 inhibitors are much
more "selective" than traditional NSAIDS; whereas drugs like ibuprofen
medicate generally, COX-2 inhibitors target specific receptors
involved in pain and inflammation.
When Celebrex came out in December of 1998, it quickly surpassed
Viagra (the "male potency pill") as the number-one prescription
drug in the nation. Patients, like Mrs. Harriet, heard Celebrex
was easier on the stomach and began requesting it from me within
months of its release. This put me in an awkward position. I'm
never comfortable prescribing a medication that has just hit the
market, no matter how many free pens I get with the drug's name
emblazoned on it. The potential complications of new medications
are rarely known until long after their release.
Alternatives still understudied
The short-term studies on Celebrex and other COX-2 inhibitors,
such as Vioxx (rofecoxib), support the claim that they are safer
than standard NSAIDs. In studies, they've been shown to cause
fewer ulcers and bleeding problems; unlike standard NSAIDs, they
do not affect the receptors on the lining of the stomach or on
platelets (blood cells that are important in clot formation).
Despite the positive reviews from early studies, there hasn't
been enough time to determine the drugs' long-term effects. Will
COX-2 inhibitors harm the kidneys over several years? What side
effects can we expect in patients who have a history of ulcers
or other medical problems that make them more susceptible to gastrointestinal
One very recent study from the University of Calgary shows that
COX-2 inhibitors may delay the healing of ulcers or other internal
bleeding tissue by blocking the pathway for prostaglandins that
are needed to stimulate the gastrointestinal tract. This means
that if you have ulcers from using traditional NSAIDs, there is
a possibility that switching to Celebrex or Vioxx may slow their
healing. Although this study was performed on laboratory rats,
not on humans, the results call for more research on the subject.
This brings me back to Mrs. Harriet. During her appointment,
she told me she was hopeful that this new medication would offer
a little relief. I carefully scanned her medication list for possible
interactions with one of the COX-2 inhibitors and asked her if
she had any allergies. I reviewed her kidney function and saw
that, like her knees, her kidneys had seen better days. Then I
gave her a small sample of Celebrex and told her to let her primary
physician closely monitor her on it. I also reminded her that
although her stomach ulcers had healed, there was no guarantee
she wouldn't have another bleeding episode or that her kidney
function wouldn't be affected.
Mrs. Harriet thanked me for my time, took hold of her four-poster
cane, and slowly walked down the exam room hallway. Her knees
thrust to the side when she planted her weight on them. I felt
a sympathetic twinge in my own knee as I watched her go.
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