In Struggle Against Alzheimer's, Hope May Be Over the
Counter
By: Denise Grady
New York Times, January 22, 2002
For people worried about developing Alzheimer's
disease, a recent study seemed to offer a rare hint of good news.
Dutch researchers found that people who took
anti-inflammatory drugs like ibuprofen or naproxen for at least two years
were only one-sixth as likely to get Alzheimer's as people who did not
take the drugs. The medicines are widely used: ibuprofen is the main
ingredient in Advil and Motrin, and naproxen is found in Aleve.
The study, published in November in The New England
Journal of Medicine, was not considered definitive, but several other
trials are under way, also testing anti-inflammatory drugs in people with
Alzheimer's disease or at high risk of developing it. The newer trials,
more rigorously designed than the Dutch one, are expected to provide
clearer answers about whether the drugs can ward off Alzheimer's.
The studies reflect scientists' growing interest in
the idea that a common condition, inflammation, may underlie many chronic
and debilitating diseases — like Alzheimer's, heart disease,
osteoporosis and diabetes — and that drugs that fight inflammation may
have a role in preventing or delaying those diseases, or at least slowing
them down.
The drugs being studied belong to the class known as
Nsaids (pronounced EN- seds) — nonsteroidal anti-inflammatory drugs. In
addition to ibuprofen and naproxen, the class includes aspirin and the
prescription drugs known as cox-2 inhibitors, celecoxib (Celebrex) and
rofecoxib (Vioxx). Prescription anti-inflammatory drugs also include
diclofenac (Voltaren), indomethacin (Indocin) and other less commonly used
drugs.
Acetaminophen (Tylenol) is not part of the group; it
treats pain and fever, but does not have the same anti-inflammatory
properties as the other drugs.
Nonsteroidal anti-inflammatories are among the most
popular medicines in America. They ease pain and fever, and millions of
people take them for headaches, backaches, arthritis, colds and the flu.
Millions with risk factors for cardiovascular disease have also been
advised to take an aspirin a day to lower the risk of a heart attack or
the most common type of stroke, which occurs when an artery supplying
blood to the brain is blocked. Aspirin is the only anti-inflammatory drug
that has been proved to have this benefit. Originally, the effect was
attributed to aspirin's ability to prevent blood clots, which can cause
heart attacks or strokes. But now, researchers think part of the
protective effect may come from aspirin's ability to quell inflammation in
the arteries, helping to prevent blockages.
But apart from recommending an aspirin a day, or a
baby aspirin, to patients at risk for heart disease, doctors are not
encouraging people to take other anti-inflammatory drugs to prevent
Alzheimer's or any other chronic illnesses. They say it is too soon: there
is no definitive evidence that the drugs will work. And regular use is not
safe for everyone.
Side effects can include stomachache or nausea in up
to 20 percent of patients, and stomach or intestinal ulcers and bleeding
in 2 percent to 4 percent of those who take the drugs for a year,
especially people over 60. The stomach bleeding can occur with little
warning, and it can be fatal. Even low doses of aspirin can cause stomach
bleeding in some people. (Cox-2 drugs are thought less likely to cause
stomach bleeding.)
Aspirin can also cause a slight increase in the risk
of a less common type of stroke, one brought on by bleeding in the brain.
In people with kidney disease, anti-inflammatory
drugs may make the problem worse.
A study has suggested — though it is not definitive
— that cox-2 drugs may cause a slight increase in heart attack risk.
Finally, researchers say that the anti- inflammatory
drugs' interactions with other drugs, including aspirin, need further
study.
Recent studies have highlighted some of the
uncertainty about the effects of long- term use of Nsaids. Last month, a
study suggested that if aspirin users took ibuprofen, too, it might cancel
out aspirin's cardiovascular benefit. The researchers, led by Dr. Garret
A. FitzGerald at the University of Pennsylvania, did the study because
they knew that many people took more than one anti-inflammatory drug at a
time.
Aspirin helps prevent heart attacks by acting on
blood cells known as platelets, which play a major role in clotting.
Aspirin prevents platelets from sticking to each other; it does so by
blocking the enzyme cyclooxygenase, or cox, and stopping production of a
substance called thromboxane, which makes platelets sticky. Aspirin's
effect on platelets is irreversible and lasts for as long as the cells
live. But the body is constantly making new platelets.
The researchers found that if people took aspirin
first, and took one dose of ibuprofen two hours later, the aspirin still
prevented their platelets from clumping. But if for six days they took
ibuprofen first, or took several doses a day after taking aspirin, the
effect of aspirin was blunted, and the platelets became sticky. Ibuprofen
temporarily attaches itself to the same part of the enzyme as aspirin,
interfering with its action.
Unlike ibuprofen, other painkillers —
acetaminophen, rofecoxib, diclofenac — did not interfere with aspirin
because the molecules have a different structure. But indomethacin might
act like ibuprofen, the researchers said.
The study, published in The New England Journal of
Medicine, was widely reported, and the findings worried many people who
take aspirin in hope of preventing a heart attack.
Dr. Leslie J. Crofford, a rheumatologist and
associate professor of internal medicine at the University of Michigan,
said some of her patients called to ask, "Will I have a heart attack
if I take an Advil?"
Dr. Crofford has been telling them that occasional
use is of no concern, especially since most people take their aspirin in
the morning.
"This idea — that if you take Advil for a
headache, it will interfere with aspirin's work — is nonsense," she
said. But she and other experts cautioned that the Pennsylvania study did
suggest that steady use of ibuprofen — several doses a day for weeks or
months at a time — might interfere with aspirin.
For patients who take aspirin to lower the risk of
heart attacks but also need regular doses of an anti-inflammatory drug,
Dr. Crofford said that she would recommend an anti-inflammatory other than
ibuprofen.
For those who like ibuprofen best for chronic pain
but also have a risk of heart attack, Dr. David P. Faxon, chief of
cardiology at the University of Chicago and president of the American
heart association, said: "They need to consult physicians. If they
need to be on a blood thinner like aspirin, they may need to switch to
another blood thinner like Plavix." Plavix is a prescription drug
that makes platelets less sticky, but it is not an anti-inflammatory.
Another article in the same issue of The New England
Journal as Dr. FitzGerald's study suggested that in people who already had
chronic kidney failure, aspirin and acetaminophen might make the condition
worse, with a slightly higher risk from acetaminophen. The drugs may block
the production of substances that are needed by the kidney. But the
researchers said that they could not be sure whether the patients' use of
anti- inflammatory drugs was a cause of kidney disease, or an effect of
it. In some of the patients, conditions that caused their kidney problems
may also have caused pain, prompting them to use painkillers more often
than healthy people.
Despite the uncertainty, though, Dr. Faxon and Dr.
Crofford warned that people with kidney failure, which in its early stages
often has no symptoms, had to be very careful in using anti-inflammatory
drugs.
But, Dr. Faxon said, "A lot of people with
kidney disease also have heart disease, and we keep them on aspirin
because the heart disease risk is worse. It's always a balancing of risks
with medicines."
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